ES2546896B1 - Method for prediction and / or prevention of overweight, obesity and / or its complications through gene expression analysis - Google Patents

Abstract

Method for the prediction and / or prevention of overweight, obesity and / or its complications by gene expression analysis. # The present invention relates to a method of prediction and / or prevention of overweight, obesity, and / or associated alterations. overweight or obesity comprising the detection of the expression product of the Lrp11 gene and also of Lrp11 in combination with certain genes. In addition, the method allows designing a personalized treatment of a subject at risk of developing these pathologies and also allows the evaluation of the effectiveness of a treatment that involves the intake of leptin. It also refers to the use of the expression products of the genes of the invention as biomarkers for said pathologies, a kit that detects said expression products and the use thereof for said indications.

Description

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Method for predicting and / or preventing overweight, obesity and / or its complications through genetic expression analysis

DESCRIPTION

The present invention relates to a method of prediction and / or prevention of overweight, obesity, and / or alterations associated with overweight comprising the detection of the expression product of the Lrp11 and Lrp11 gene in combination with certain genes. Said method also allows monitoring the effectiveness of feeding with breast milk or formula containing leptin, in the reversal of the predisposition detected. Therefore, the invention could be framed in the field of the agri-food industry.

STATE OF THE TECHNIQUE

In general, changes in lifestyle in developed countries, particularly a higher consumption of fats or foods of high energy density, associated with a lower physical exercise, have been considered as one of the main causes of the increase in incidence of metabolic disorders. It is known that obesity has a genetic component and an environmental component, and there is also evidence that the environment, nutrition and feeding in early stages of life is able to metabolically program the newborn affecting the propensity to suffer different types and degrees of overweight / obesity and other related diseases at later ages (Godfrey and Barker, Am J Clin Nutr, 2000, 71 (5 Suppl): 1344S-1352S). Such metabolic programming goes beyond the genetic factor and affects the development of key organs and tissues, leading to a different predisposition to overpressure and its metabolic complications during the normal aging process. There are epidemiological evidences that evidence this association, such as the emblematic study on the Dutch famine. This study showed that men whose mothers suffered malnutrition during the first and second trimester of pregnancy, due to the famine that hit the West during the Second World War, had a higher prevalence of obesity in adulthood (Ravelli et al. , N Engl J Med 1976, 295 (7): 349-353). Likewise, a low birth weight has been associated with a greater propensity to be overweight in adulthood (Godfrey and Barker, Am J Clin Nutr, 2000, 71 (5 Suppl): 1344S-1352S). Model Studies

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Animals have also shown evidence that caloric restriction during the gestation period has negative effects on offspring, and in particular, increases their susceptibility to developing overweight / obesity in adulthood and other related metabolic alterations, especially insulin resistance and leptin, as well as heart disease, type 2 diabetes, hypertension, musculoskeletal and respiratory disorders, among others (Anguita et al., RM, J Nutr, 1993, 123 (8): 1421-1428; Jones and Friedman, Science, 1982, 215 (4539): 15181519; Jones et al., J Nutr, 1984, 114 (8): 1484-1492; Bray and Bellanger, Endocrine, 2006, 29 (1): 109-117; and Smith, Am J Med., 2007, 120 (3 Suppl 1): S3-S11). More specifically, results obtained in rats in studies carried out in the Laboratory of Molecular Biology, Nutrition and Biotechnology (LBNB) of the University of the Balearic Islands have shown that only 20% of maternal caloric restriction during the first half of pregnancy leads to development of overweight and other disorders, including insulin and leptin resistance, in adulthood (Palou et al., Nutr Metab, 2010, 7: 69-79; Palou et al., J Nutr Biochem, 2012, 23: 1627 -1639). In addition, these animals have hyperphagia, or excessive intake, as well as an increase in their preference for fat-rich foods, compared to animals in the control group (Palou et al., Nutr Metab, 2010, 7: 69-79). These alterations in eating behavior can be explained by alterations of the hypothalamic structures responsible for the control of intake, and in particular of the arcuate nucleus and the paraventricular nucleus (Garcia et al., Diab Obes Met, 2010, 12 (5): 403 -413; Konieczna et al., PlosOne, 2013, 8 (11): e81906).

On the other hand, although it is known that nutritional alterations should be at the base of this type of problem, much less was known that nutrients or specific components of food could be the main responsible. In recent years, leptin has been identified as one of them (Miralles et al., Obesity, 14 (8): 1371-1377; Pico et al., Int J Obes, 2007, 31 (8): 1199-1209 ; Sanchez et al., Endocrinology, 2008, 149 (2): 733-740). Several studies show that breastfeeding, compared to artificial lactation (infant formula), is associated with a lower risk of suffering various complications in adulthood, including overweight and obesity (Armstrong and Reilly, Lancet, 2002, 359: 2003-2004; Gillman et al., Jama., 2001,285: 2461-2567; Kramer, J. Pediatr, 1981, 98: 883-887; von Kries et al., Bmj, 1999, 319: 147-150).

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The identification and characterization of new early and solid biomarkers is crucial to be able to make personalized nutritional recommendations and interventions, before the nutritional problem is manifested, while they can serve as a basis for the food industry as a crucial tool in scientific substantiation. of health declarations in foods related to the prevention of obesity, overweight and their co-morbidities.

DESCRIPTION OF THE INVENTION

The present invention demonstrates that changes in the expression profile of the Lrp11 gene and also changes in the expression profile of Lrp11 and other specific genes in the blood cells are associated with the risk of developing overweight, obesity or other disorders or alterations or related diseases or pathologies. In addition, such changes are observed at an early age of development, before the disease has manifested. The expression profile of these specific genes can therefore be used as an early biomarker of higher risk of these pathologies, which allows preventing their development and also of pathologies associated with obesity.

The use of transcriptomic analysis of Lrp11 and also of Lrp11 is demonstrated in conjunction with other specific genes in blood cells of an organism, obtained and isolated at birth or at another stage of life, preferably in early stages, during development, it is useful as a biomarker of risk or tendency that in the future these subjects will have the ability to accumulate excessive fat in some part (s) of their body and / or develop overweight, obesity and / or pathologies or other associated disorders or disorders. In addition, the present invention also allows the identification of those subjects who, although susceptible to such alterations, can prevent their appearance by feeding with breast milk or with a leptin supplement during the lactation period by analyzing the expression of the Lrp11 gene and the Lrp11 gene in conjunction with other specific genes in an isolated biological sample.

The present invention also allows monitoring subjects at high risk of obesity and their related complications to establish the success of a leptin treatment in a subject by detecting and / or quantifying the expression of the Lrp11 gene as! as by the detection and / or quantification of the expression of the Lrp11 gene in combination with other specific genes. The invention identifies whether

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These individuals have reversed their predisposition to these diseases by analyzing the transcriptomic profile of blood cells after feeding with breast milk or formula supplemented with leptin, or with any other adequate diet provided by said leptin during the period of breastfeeding in the form of food or supplement. In a specific embodiment, the invention relates to the identification of subjects predisposed to the diseases described above and that have reversed said predisposition by analyzing mRNA expression of Lrp11 and Lrp11 in combination with groups of specific genes in blood cells. after feeding with breast milk or formula milk supplemented with leptin, or with any

food provided by said leptin during the period of breastfeeding.

In another particular embodiment of the invention it is intended to analyze the mRNA expression of Lrp11 and Lrp11 in combination with specific genes whose expression was altered in a previous analysis, after feeding the individuals with breast milk or formula supplemented with leptin milk , or with any

food provided by said leptin during the period of breastfeeding. Thus, the invention makes it possible to identify the success of the risk reversion of developing overweight, obesity and / or associated pathologies. Therefore, another aspect of the invention makes it possible to identify if an individual has reverted quite safely his predisposition to the disorders defined above by transcriptomic analysis of these genes in blood cells after feeding with breast milk or supplemented formula milk with leptin, or with any other adequate diet provided by said leptin during the period of breastfeeding. In the present invention it is demonstrated that if Lrp1 alone or in conjunction with a plurality of the genes described in Table 1 (up to a total of 218 genes) have restored their genetic expression with respect to the previous altered state, which they presented in the analysis prior to Feeding with leptin during the period of breastfeeding, the individual has reversed their predisposition to the diseases specified above. Another specific embodiment of the invention allows, therefore, that in the absence of reversion, alternative intervention strategies can be established with the intention of preventing the development of diseases against which individuals have a high risk of suffering them later.

The advantages presented by the present invention are:

- Allows the identification of individuals at high risk of being overweight or

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Obesity or other related disorders at an early age, even before any increase in weight or fat or pathological symptoms prior to the disease or disorders referred to develops, allowing for more effective intervention.

- It allows early intervention to prevent the development of the disease by feeding these individuals with breast milk or formula milk supplemented with leptin, or with any other adequate feeding provided by said leptin during the period of breastfeeding.

- It allows individuals to be monitored to determine if they have reversed the risk of developing the disease after being fed with breast milk or formula milk supplemented with leptin, or with any other adequate diet provided by said leptin during the period of breastfeeding.

By "lactation period" in the context of the present invention is understood as the first months of life of a mammalian animal, and in particular although a human is not exclusive.

By "exclusive breastfeeding" is meant feeding a child or infant girl up to six months of age exclusively with breast milk.

By "early age" in the context of the invention is understood as the stage of life that comprises from the fetal stage to adolescence.

In another aspect, the invention relates to the analysis of the profile of genetic expression of blood cells to identify the subjects susceptible to developing the harmful effects that a nutritional restriction entails during the fetal stage or other adverse conditions during the prenatal stage, which are without being exclusive. : overweight, obesity, hyperphagia, type 2 diabetes, insulin resistance, leptin resistance, dyslipidemia, etc. In a particular form of the present invention it refers to a caloric restriction during the gestation stage.

Therefore, a first aspect of the invention relates to a method of obtaining useful data for the prediction and / or prevention of overweight, obesity and / or its complications comprising the detection and / or quantification of an expression product of the Lrpllen gene an isolated biological sample of a subject. Hereinafter, we will refer to this as the "first method of the invention".

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By "overweight" or excess weight is the excessive accumulation of body fat, which appears when the intake exceeds energy expenditure. Overweight in the context of the invention means all overweight, from mild overweight (body mass index, BMI> 25) to clinically manifest obesity (BMI> 30). Therefore, obesity is understood as the excessive accumulation of fat that is associated with a BMI> 30.

By "complications" (or also called "pathologies associated with overweight", "associated complications", "associated alterations" or "co-morbidities") means any pathology that may be associated with a state of overweight or obesity. Non-limiting examples of these pathologies are: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications.

The term "subject," as used herein, refers to all animals classified as mammals and includes, but is not restricted to, domestic and farm animals, primates and humans, for example, humans, nonhuman primates, cows. , horses, pigs, sheep, goats, dogs, cats, or rodents. Preferably, the subject is a human male or female of any race.

The term "biological sample" includes, but is not limited to, tissues and / or biological fluids of an individual, obtained by any method known to a person skilled in the art that serves this purpose. The biological sample may comprise blood cells. "Blood cells" means whole blood cells, peripheral blood mononuclear cells (PBMCs) or any blood cell with its own genetic material and expression capacity that can be isolated from the bloodstream. It is also understood cells that besides being able to be found in the blood can also be found in any other biological sample, such as in saliva or tissues. Said sample can be obtained by different methods previously described and known to the person skilled in the art. Blood samples include, for example, peripheral blood, cardiac blood and umbilical cord blood samples.

The term "prevention" as understood in the present invention is to prevent the occurrence of the disease or alterations referred to, that is, to prevent

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the disease or the pathological condition or anomaly in a subject (preferably mammal, and more preferably a human), in particular that acquires predisposition to develop the aforementioned alterations, ie obesity, overweight and its complications.

A preferred embodiment of the first aspect of the invention relates to the method in which an expression product of the Gls and / or Ubash3b gene is also detected and / or quantified. In an even more preferred embodiment, the Lrp11, Gls and Ubash3b genes are detected and / or quantified.

In a more preferred embodiment, an expression product of at least one of the genes selected from the list comprising: Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x, or any combination thereof, is detected and / or quantified. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x genes is detected and / or quantified.

In another preferred embodiment of the first aspect of the invention, the method further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1 , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any combination thereof. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a genes is detected and quantified , Myo3b, Myt1, Aloxe3 and Grm6.

In another even more preferred embodiment of the first aspect of the invention, the method further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtc1 Olr1075 Ctla2a Olr1500 Txnip Bcap29 Stk4 Myc Tsc22d3 Msh4 Zc3h15 Uri1 Il10 Zfp503 Ldlrap1 Cirh1a Acp6 Olr1394 Osbpl1a Cd2 Cd2 , Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a genes is detected and quantified , Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10,

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Zfp503, Ldlrapl, Cirhla, Acp6, Olr1394, Osbplla, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19.

In another even more preferred embodiment of the first aspect of the invention, the method further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising the genes described in Table 7. Preferably, an expression product of the genes described in Table 1 is detected and / or quantified.

In another even more preferred embodiment of the first aspect of the invention it refers to the method for the prediction and / or prevention of complications associated with overweight or obesity are selected from the list comprising: type 2 diabetes, insulin resistance, resistance to leptin, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications.

By "type 2 diabetes" or "type 2 diabetes mellitus" is meant a metabolic disease characterized by high blood glucose levels with alterations of the insulin system.

By "insulin resistance", also called insulin resistance, a physiological condition is understood in which the cells do not respond to the normal actions of the hormone insulin.

"Leptin resistance" means a physiological condition in which cells do not respond to the normal actions of the hormone leptin.

By "hyperphagia" is meant an excessive increase in appetite sensation and exceeded food intakes.

By "dyslipidemia" or "dyslipidemia" means a series of pathological conditions whose common element is an alteration of the metabolism of lipids, with their consequent alteration of the conditions of lipids and lipoprotins in the blood. Preferably, dyslipidemia means hypercholesterolemia and hypertriglyceridemia.

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By "hypercholesterolemia" is meant the presence of high levels of cholesterol in the blood.

By "metabolic syndrome", also known as "syndrome X", "plurimetabolic syndrome", or "insulin resistance syndrome", is meant the combination of several diseases or risk factors in the same individual that increase their likelihood of suffering from cardiovascular disease or diabetes mellitus

By "fatty liver", also known as "hepatic steatosis", is meant a multifactor metabolic disorder that derives from the accumulation of fat in the liver without relation to alcohol consumption.

By "hypertension" or "arterial hypertension" is meant a chronic disease characterized by a continuous increase in blood pressure figures in the arteries.

"Cardiovascular disease" means all types of diseases related to the heart or blood vessels.

By "obstructive sleep apnea", "apnea-hypopnea syndrome during sleep", "hypersomnia and periodic breathing syndrome" or "Pickwick syndrome associated with obesity" are understood respiratory disorders that occur during sleep and are characterized for repeated episodes of obstruction or collapse of the upper airway, because the airway narrows, becomes blocked or becomes flexible.

By "cancer" is meant a disease caused by a group of cells that multiply uncontrollably and autonomously, invading other tissues locally and remotely.

"Arthritis" means the existence of inflammation in some joint.

By "osteoarthritis", also called "osteoarthritis" is meant a disease caused by wear of the cartilage, a tissue that acts as a buffer when protecting the ends of the bones and that favors the movement of the joint.

"Psychiatric complications" associated with obesity are those psychiatric complications that may occur as a result of obesity, among which are low self-esteem, social isolation, anxiety, depression, emotional disorders, etc.

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A second aspect of the invention relates to an in vitro method for prediction and / or prevention of overweight, obesity and / or its complications in a subject comprising:

to. the detection and / or quantification of an expression product of the Lrp11 gene in a biological sample isolated from a subject;

b. the association of the detection of a significant alteration of the expression to a bad prognosis.

Hereinafter, we will refer to this as the "second method of the invention."

The term "in vitro" refers to the method of the invention being performed outside the subject's body.

In the present invention it is shown that, for example, in the case of the Lrp11 gene, an increase in the expression of this gene in relation to a control reference value is associated with a poor prognosis.

A preferred embodiment of the second aspect of the invention relates to the method which further comprises comparing the data obtained from the biological sample isolated from a subject of step (a), with reference expression values, for example a control, so that if there is a significant difference, the expression product is considered altered and said alteration is associated with a poor prognosis. Said alteration can be either a significant increase (overexpression) or a significant decrease (subexpression). The alteration can be determined by the "fold change" determined by any method known to the person skilled in the art.

The term "mRNA expression profile analysis" as understood in the present invention refers to a quantitative or semi-quantitative analysis of mRNA expression levels of genes by the following currently available methodologies, without being exclusive of each other: expression microarray, SAGE (Serial Analysis of Gene Expression, or Serial Analysis of Gene Expression), RT-PCR (quantitative or semi-quantitative), Northen Blot, Dot Blot, etc. In a particular embodiment, the expression levels of the mRNA of the target genes

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Selected are determined by quantitative PCR, preferably real-time PCR.

To normalize the mRNA expression values between the different samples, it is possible to compare the mRNA expression levels of interest in the samples to be tested with the expression of a reference RNA. A "reference RNA" as used herein, refers to an RNA whose expression levels do not change or only change in limited amounts between different individuals, for example between a control subject and a subject likely to suffer from obesity in age. adult Preferably, the reference RNA is mRNA derived from maintenance genes and encoding proteins that are constitutively expressed and that perform essential cellular functions. Examples of maintenance genes for use in the present invention include 18S, GDI1, GAPDH, SURF4, PSMA6 and p-actin. In one embodiment, the quantification of the relative genetic expression is calculated according to the comparative method Ct using the reference gene as an endogenous control. The final results are determined according to the previously described formula 2-ACt (Pfaffl, Nucleic Acids Res, 2001.29 (9): e45).

It is understood as "poor prognosis" in the present invention to the increased risk of developing overweight, obesity and / or associated diseases. Understanding by "good prognosis" therefore, the opposite.

In a preferred embodiment of the second aspect of the invention, also in step a) a Gls and / or Ubash3b expression product is detected and / or quantified; and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. Preferably, in step a) an expression product of Lrp11, Gls and Ubash3b is detected and / or quantified; and in stage b) the alteration of the expression of said genes is associated with a poor prognosis.

In another preferred embodiment of the second aspect of the invention, also in step a) an expression product of at least one of the genes selected from the list comprising: Crmp1, Gla, Paox, Rnf10 is detected and / or quantified. , Selenbp1 and Tmsb4x, or any of its combinations and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. Preferably, the genes detected and / or quantified and whose alteration of expression is associated with a

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Bad prognosis are Lrp11, Gls, Ubash3b, Crmpl, Gla, Paox, Rnf10, Selenbpl and Tmsb4x.

In another preferred embodiment of the second aspect of the invention, also in step a) an expression product of at least one of the genes selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1 is detected and / or quantified , Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any of their combinations and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. Preferably the genes detected and / or quantified and whose alteration of the expression is associated with a poor prognosis are Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1 , Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6.

In another preferred embodiment of the second aspect of the invention, in addition to step a) an expression product of at least one of the genes selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtc1 is detected and / or quantified Olr1075 Ctla2a Olr1500 Txnip Bcap29 Stk4 Myc Tsc22d3 Msh4 Zc3h15 Uri1 Il10 Zfp503 Ldlrap1 Cirh1a Acp6 Olr1394 Osbpl1a Cd2 Cd2 , Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any of their combinations and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. Preferably, the genes detected and / or quantified and whose alteration of expression is associated with a poor prognosis are: Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1 , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Z3103, Mh4, Z3p3, Mh4, Z3p3, Mh4, Z3p3, Md4, 3, M3 , Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19.

In another preferred embodiment of the second aspect of the invention, also in step a) an expression product of at least one of the genes selected from the list comprising the genes described in Table 7 and is detected and quantified. in stage b) the alteration in the expression of said genes is associated with a poor prognosis. Preferably, in step a) an expression product of the genes described in Table 1 is detected and / or quantified and in step b) an alteration in the expression of said genes is associated with a poor prognosis.

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In an even more preferred embodiment of the second aspect of the invention, complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis, and psychiatric complications.

A third aspect of the present invention relates to an in vitro method for designing an individualized treatment for a subject comprising detecting and / or quantifying the expression product of the Lrp11 gene in a biological sample; in which the alteration of the expression is indicative that the treatment to be administered is leptin or a composition comprising leptin. Hereinafter, we will refer to this as the "third method of the invention".

In a preferred embodiment of the third aspect of the present invention, an expression product of the Gls and / or Ubash3b genes is also detected and / or quantified. Preferably, an expression product of the Lrp11, Gls and Ubash3b genes is detected and quantified and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin.

In another preferred embodiment of the third aspect of the present invention, an expression product of at least one of the genes selected from the list comprising Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x is also detected and / or quantified. or any of its combinations and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x genes is detected and quantified and where the alteration of the expression of said genes is indicative that the treatment to be administered it is leptin or a composition comprising leptin.

In another more preferred embodiment of the third aspect of the present invention, the method also comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1 , Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and

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Grm6, or any combination thereof and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmpl, Gla, Paox, Rnf10, Selenbpl, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5 genes is detected and / or quantified , Myo3b, Myt1, Aloxe3 and Grm6 and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin.

In another even more preferred embodiment of the third aspect of the present invention, the method further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Itgal, Prm1, Pcmtd2, crtc1, Olr1075, Ctla2a, Olr1500, TXNIP, Bcap29, STK4, Myc, Tsc22d3, MSH4, Zc3h15, uri1, IL10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, CD2, Bcl2, Meis3, Serpinf2, pkiA, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a genes is detected and quantified , Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfpr1, Acf1501, Acf1501, Acf1501 , Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19 and where the alteration of the expression of these genes is indicative that the treatment to be administered is leptin a composition comprising leptin.

In an even more preferred embodiment of the third aspect of the present invention, the method further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising the genes described in Table 7. and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. Preferably, a gene expression product described in Table 1 is detected and / or quantified and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin.

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In an even more preferred embodiment of the third aspect of the present invention the composition comprising leptin is breast milk.

In another even more preferred embodiment of the third aspect of the present invention, complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, hypertriglyceridemia dyslipidemia, hypercholesterolemia, metabolic syndrome, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications.

A fourth aspect of the invention relates to an in vitro method of evaluating the effectiveness of a treatment with leptin or a composition comprising leptin comprising the detection and / or quantification of an expression product of the Lrp11 gene in a biological sample. isolated from a subject who has received such treatment.

In a preferred embodiment of the fourth aspect of the present invention, the expression product of the Gls and / or Ubash3b genes is also detected and / or quantified. Preferably, the expression product of the Lrp11, Gls and Ubash3b genes is detected and / or quantified.

In a more preferred embodiment of the fourth aspect of the present invention, an expression product of at least one of the genes selected from the list comprising Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x is also detected and / or quantified. , or any of its combinations. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x genes is detected and / or quantified.

In an even more preferred embodiment of the fourth aspect of the present invention, the method also comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any combination thereof. Preferably, an expression product of the Lrp11, Gls, Ubash3b genes is detected and quantified,

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Crmpl, Gla, Paox, Rnf10, Selenbpl, Tmsb4x, Smagp, Diexf, Gabra6, Fycol, Fosll, Bucsl, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6.

In another even more preferred embodiment of the fourth aspect of the present invention, the method also comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Itgal, Prm1, Pcmtd2, crtc1, Olr1075, Ctla2a, Olr1500, TXNIP, Bcap29, STK4, Myc, Tsc22d3, MSH4, Zc3h15, uri1, IL10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, CD2, Bcl2, Meis3, Serpinf2, pkiA, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof. Preferably, an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, genes is detected and quantified Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfp501, Llpa1, Ldl1, Lcp1501, Ldl1, Acl1, Circ1, Ldl1, Lcp1501 Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19.

In another even more preferred embodiment of the fourth aspect of the present invention, the method further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising the genes described in Table 7. Preferably, an expression product of the genes described in Table 1 is detected and / or quantified.

By "expression product" is meant messenger RNA (mRNA) or protein.

An even more preferred embodiment of the first, second, third and fourth aspect of the present invention relates to said methods where the expression product is mRNA.

In an even more preferred embodiment of the first, second, third and fourth aspects of the present invention, the biological sample is selected from the list comprising blood, peripheral blood, cardiac blood, umbilical cord blood, saliva, urine and lymph.

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In another even more preferred embodiment of the first, second, third and fourth aspects of the present invention, the subject is a neonate.

In another even more preferred embodiment of the first, second, third and fourth aspects of the present invention, the subject is a human.

The subject in the present invention may have suffered nutritional restriction.

"Nutritional restriction" means the daily limitation of the intake of a nutrient below the baseline nutritional needs, be it the total energy limitation or caloric or energetic restriction, the limitation of one or more macronutrients, specifically carbohydrates, proteins and / or lipids, the limitation of one or more micronutrients, such as vitamins, minerals, etc., or any combination of the above. The nutritional restriction may have suffered during the fetal stage.

By "fetal stage" or "gestation stage" is understood the time that elapses between the time of conception and childbirth, considering the entire period or only a fragment of said period.

A fifth aspect of the present invention refers to the use of the Lrp11 gene expression product as a biomarker for prediction and / or prevention of overweight, obesity and / or its complications in a subject.

By "biomarker" is meant the characteristic that is objectively quantifiable and evaluable as an indicator of normal biological processes, pathological processes or response to a therapeutic intervention.

A preferred embodiment of the fifth aspect of the invention relates to the use which also includes the use of the expression product of the Gls and / or Ubash3b genes. Preferably the genes are Lrp11, Gls and Ubash3b.

A more preferred embodiment of the fifth aspect of the invention refers to the use that also includes the use of the genes selected from the Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x list, or any combination thereof. Preferably the genes are: Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x.

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An even more preferred embodiment of the fifth aspect of the invention refers to the use that also includes the use of genes are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b , Myt1, Aloxe3 and Grm6, or any combination thereof. Preferably the genes are Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Mytm, Aloxe, Gr.

An even more preferred embodiment of the fifth aspect of the invention refers to the use that also includes the use of genes are selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4 , Myc, Tsc22d3, MSH4, Zc3h15, uri1, IL10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, pki, Cd40lg, SLC9A3R1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, TGM1 and Rps19, or any of its combinations. Preferably, the genes are Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b3, Myt1, Alotm, Grt , Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfp503, Ldlrap1, Cirh1a, Acp6, Old3, B2 , Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19.

Another even more preferred embodiment of the fifth aspect of the invention relates to the use which also includes the use of the genes described in Table 7. Preferably the genes described in Table 1.

Another even more preferred embodiment of the fifth aspect of the invention relates to the use where the expression product is mRNA.

Another even more preferred embodiment of the fifth aspect of the invention relates to the use where complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome , fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications.

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Another even more preferred embodiment of the fifth aspect of the invention relates to the use where the subject is a newborn.

Another even more preferred embodiment of the fifth aspect of the invention relates to the use where the subject is a human.

A sixth aspect of the invention relates to a kit comprising primers, probes and / or specific antibodies to detect and / or quantify an expression product of the Lrp11 gene. Preferably, the expression product of the Gls and / or Ubash3b genes is also detected and / or quantified, more preferably the expression product of the Lrp11, Gls and Ubash3b genes is detected and / or quantified.

A preferred embodiment of the sixth aspect of the invention relates to a kit that also comprises specific primers, probes and / or antibodies to detect and / or quantify an expression product of at least one of the genes that are selected from the list comprising : Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x, or any combination thereof. Preferably of the genes Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x.

Another preferred embodiment of the sixth aspect of the invention relates to a kit which also comprises primers, probes and / or specific antibodies to detect and / or quantify an expression product of an expression product of at least one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any combination thereof. Preferably of the genes Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe, Gr.

Another preferred embodiment of the sixth aspect of the invention relates to a kit that also comprises primers, probes and / or specific antibodies to detect and / or quantify an expression product of the genes that are selected from the list comprising: Itgal, Prm1 Pcmtd2 Crtc1 Olr1075 Ctla2a Olr1500 Txnip Bcap29 Stk4 Myc Tsc22d3 Msh4 Zc3h15 Uri1 Il10 Zfp503 Ldlrap1 Cirh1a Acp6 Olr1394 Cd2 , Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof. Preferably of the genes Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10,

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Selenbpl, Tmsb4x, Smagp, Diexf, Gabra6, Fycol, Fosl 1, Bucsl, Chrnd, Cacnalc, Slc7a5, Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Tpx2, Oliva, Tb2, 292 , Myc, Tsc22d3, MSH4, Zc3h15, uri1, IL10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, pki, Cd40lg, SLC9A3R1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, TGM1 and Rps19.

Another even more preferred embodiment of the sixth aspect of the invention relates to a kit that also comprises primers, probes and / or specific antibodies to detect and / or quantify an expression product of at least one of the genes that are selected from the list which comprises the genes described in table 7. Preferably it comprises primers, probes and / or specific antibodies for detecting and / or quantifying an expression product of the genes described in table 1.

Another preferred embodiment of the sixth aspect of the invention relates to the kit where the expression product is mRNA.

A seventh aspect of the present invention relates to the use of the kit of the sixth aspect of the invention for the prediction and / or prevention of overweight, obesity and / or its complications in a subject.

An eighth aspect of the present invention relates to the use of the kit of the sixth aspect of the invention to design an individualized treatment useful for the prediction and / or prevention of overweight, obesity and / or its complications in a subject.

A ninth aspect of the present invention relates to the use of the kit of the sixth aspect of the invention for the evaluation of the effectiveness of a leptin treatment in a subject.

A preferred embodiment of the seventh, eighth and ninth aspects of the invention relates to the use where complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, hypertriglyceridemia dyslipidemia, hypercholesterolemia, syndrome Metabolic, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications.

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Another preferred embodiment of the seventh, eighth and ninth aspects of the invention relates to the use where the subject is a newborn.

Another preferred embodiment of the seventh, eighth and ninth aspects of the invention relates to the use where the subject is a human

Throughout the description and the claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will be derived partly from the description and partly from the practice of the invention. The following examples and figure are provided by way of illustration, and are not intended to be limiting of the present invention.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1. Summary of the main processes in which the 224 genes that have undergone changes in their genetic expression are involved in the PBMCs of 25-day rats as a result of maternal caloric restriction during gestation.

EXAMPLES

The invention will be illustrated below by tests carried out by the inventors, which demonstrates the effectiveness of the present invention.

Material and methods:

General procedure for selecting the groups of rats to study

Rats of rats subjected to caloric restriction were studied during gestation (as a group more prone to develop obesity), and treated during lactation with physiological doses of leptin. To obtain them, female vlrgenes Wistar rats of about 200-250g were crossed with male rats. The conception success was determined by checking the presence of sperm after a vaginal smear. After mating and confirmed conception, each female was placed in an individual cage with free access to water. The rats were kept in a temperature controlled room

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(22 ° C) and a 12-hour light-dark cycle. A first group of control rats (n = 7) remained with free access to standard feed (3000 Kcal / Kg).

A second group of rats was subjected to a caloric restriction of 20%, with respect to the group of control mothers, during the first 12 days of gestation (n = 10), considering the conception day as day 0. After these 12 days of food restriction left them free access to feed. On the first day of birth, the number of crlas was adjusted to 10 per mother, and they were randomized into two groups: a group that was treated with the vehicle and a group that was treated with leptin. Specifically, from day 1 to day 20 of breastfeeding, and during the first two hours of the light cycle, it was supplied daily and orally, using a pipette, 20 pL of the vehicle (water) to the CR group or a solution of murine leptin dissolved in water to the leptin-treated group (CR-Leptin). The amount of leptin given to animals was gradually increasing from 1 ng of leptin on day 1 to 43.8 ng of leptin on day 20; amounts that were calculated to provide five times the average amount of daily leptin intake taken from breast milk (Pico et al., Int. J. Obes., 2007, 31 (8): 1199-1209).

Crlas of the control mothers, called the control group, also received 20 pL of the vehicle (water) daily from day 1 to day 20 of life. After weaning, on day 21, all the crlas were fed a normolipldica diet until they were slaughtered at the age of 25 days.

Ace! therefore, samples from three groups of male rats were studied: cribs of mothers fed ad libitum (controls) (n = 10-11), rats of rats subjected to heat restriction during the first half of pregnancy (CR) (n = 10-11) and CR crusts supplemented daily with a physiological dose of leptin orally throughout lactation (CR-Leptin) (n = 10-11).

During the study period, the monitoring of body weight and intake was carried out. On the day of the sacrifice, blood samples were collected for subsequent plasma collection and isolation of PBMCs. An array of the entire genome was made.

General procedure of the analysis of the profile of genetic expression of PBMCs by microarrays.

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The isolation of the RNA samples from the PBMCs was carried out by extraction with EZNA® TOTAL RNA kit I columns (Omega Bio-Tek Inc., Norcross, GA, USA) following the commercial instructions.

RNA samples were analyzed in the Agilent 2100 Bioanalyzer with RNA 6000 Nano chip (Agilent Technologies, South Queensferry, United Kingdom). To ensure high RNA quality, only samples with an RNA integrity number (RIN)> 8 were used for the microarray (n = 8 / group). Then, 0.08 qg of RNA from each sample was retrotranscribed to complementary DNA (cDNA) using the Agilent Low Input Quick Amp Labeling kit (Agilent Technologies, Inc., CA, USA), following the manufacturer's protocol. Half of the cDNA of each sample was used for linear amplification of the cRNA and labeling with cyanine-3 (Cy3) or Cy5. The transcription and labeling conditions were: 40 ° C for 2 h. Then the labeled and amplified cRNA was purified using the Qiagen Rneasy MiniSpin columns (Qiagen, Madrid, Spain). The incorporation of the labeling and the concentration of RNAc was quantified by NanoDrop ND 1000 spectrophotometer (NanoDrop Techonologies, Ins., Wilmington, DE). Of the 24 samples, 20 were selected for microarray analysis. Next, 825 ng of cRNA of each sample labeled with Cy5 and 825 ng of a mixture of the cRNA of all samples, labeled with Cy3, were hybridized in the Agilent microarrays of the entire 4x44K G4131F rat genome (Agilent Technologies, Inc ., Santa Clara, CA, USA) for 17 h at 65 ° C in hybridization chambers inside an agitation oven at 10 rpm (Agilent Technologies). Then, the arrays were washed with "GE wash buffer 2" for 1 min at 37 ° C, followed by acetonitrile for 1 min at room temperature, and finally they were plated with a stabilizing solution and dried for 30 min at room temperature following the manufacturer's instructions (Agilent Technologies).

The arrays were scanned with Agilent Microarray Scanner (Agilent Technologies). The signal intensity of each spot was quantified and the raw data was extracted using Feature Extraction Software version 10.10.1.1 (Agilent Technologies). The fund was corrected using Babelomics (Medina et al., Nucleic Acids Res, 2010, 38: W210-W213), a set of web tools for microarray data analysis. The differences in the gene expression between the different groups of animals, CR vs controls; CR vs CR-Leptin; CR-Leptin vs controls, was carried out using the Limma package (Smyth, Stat. Appl. Genet. Mol

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Biol, 3, Article3, 2004) of Bioconductor (Gentleman et al., Genome Biol, 5 (10), R80, 2004), implemented on the Babelomics web platform. The Limma methodology performs the t-statistic that is calculated for each gene; including the values of p and the values of multiple change or fold changes (FC) in English. The threshold of significance was set at p <0.010. Next, the list of genes with statistics was analyzed manually according to their biological information, obtained using the available databases (Genecards, KEGG, NCBI, Reactome, UniProt, USCN, WikiPathways) based on the key biological domains, as their function molecular and biological process. All genes were assigned to different biological processes according to their function.

Example 1. Changes in the transcriptomic profile of PBMCs after a maternal caloric restriction during pregnancy.

In the microarray analysis 45220 probes were tested (4x44K G2519F; Agilent Technologies). In total, the expression of 473 genes was significantly different between the animals of the Control group and those of the CR group. Of these, 249 were classified as unknown and therefore were not taken into account for the following analysis. Of the remaining 224, 166 were overexpressed and 58 under-expressed in the CR group regarding controls. The main processes in which these genes were involved can be included in: transcriptional and translational machinery, immune system, signaling, cell turnover, protein and polyamine metabolism, transport, lipid metabolism, etc. (Figure 1).

Table 2 shows the list of the 224 genes that had their expression altered in the animals of the CR group with respect to the control group, including the significance value p and the FC (with respect to the control group) for each gene resulting from the statistical analysis accomplished. A positive HR value indicates overexpression in the CR group with respect to the control group (166 genes) and a negative FC value indicates subexpression in the CR group with respect to the control group (58 genes).

These results show that maternal caloric restriction during pregnancy is capable of producing changes in the gene expression profile of the PBMCs of the offspring at an early age, prior to the appearance of the alterations described in adulthood for these animals. Therefore, the alteration of the gene expression profile of these genes in the blood cells can be used as a tool to identify early biomarkers of disease.

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Example 2. Leptin treatment

Of the 224 genes whose expression was altered as a result of maternal caloric restriction during pregnancy (table 2), 218 restored total or partial normality in the CR-Leptin group (see table 1). A total of 22 genes resulted in a total reversion (table 5) and they did so partially 196. Therefore, these results confirm that leptin treatment is capable of reversing the negative effects associated with energy restriction during the fetal stage.

Table 1 shows, first, the 218 genes that restored total or partial normality in the CR-Leptin group. The first 22 are those that significantly re-established their expression in the animals of the CR-leptin group with respect to the CR group, including the value of significance and the FC (with respect to the CR group) specific to each gene, resulting from the statistical analysis performed (collected in table 5). The following 196 genes correspond to those that partially restored their expression in the animals of the CR-Leptin group with respect to the CR group, including the significance value and the FC (with respect to the CR group and with respect to the control group) of each gene, resulting of the statistical analysis performed. In addition, the IRX3 gene that shows a pattern of similar changes is included, without reaching the threshold of statistical significance of the previous ones, due to its biological plausibility more clearly associated with obesity, compared to any other gene described to date. Also included are the value of significance and the FC comparing the CR vs Controls group. For each of the comparisons, a positive HR value indicates overexpression and a negative HR value indicates subexpression. As an example, in the case of Lrp11, overexpression occurs in the CR group with respect to the control group, and this overexpression reverts with leptin treatment.

The selection and prioritization of the genes was carried out according to the value of the "p" when comparing the expression levels between the control group and the CR group, according to the results of the microarray. Now, among the 22 genes in which we find a total reversion in the levels of expression with the treatment with leptin (table 5), and all of them with a very good "p", the prioritization has also taken into account those that were easily quantifiable by RT-qPCR (ie that the expression was detected with an RT-qPCR made under normal conditions, without having to use particular conditions to increase the sensitivity), and that the expression pattern described in the males was the same also in the females. This allowed us to select 9

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genes (table 4) within the group of 22 (table 5) that follow a similar pattern in males and females and in which it is observed, when doing a joint analysis in both sexes, a reversion with leptin treatment. Also, within these

9 genes, which show a similar pattern in males and females, were selected a group of 3 genes (table 3) that were for both males and females, analyzed separately, obtained a more significant value for RT-qCRP, both when comparing the CR group with the control, as when comparing the CR-Leptin group with the CR. Within the group of the three mentioned genes, it was observed that the Lrp11 gene was the best in terms of its associated "p".

These results are surprising, since previous studies carried out in the LBNB research group showed that rat rats subjected to caloric restriction during gestation acquire a greater propensity to develop obesity and associated metabolic alterations in adulthood (Palou et al ., Nutr Metab, 2010, 7: 69-79; Palou et al., J Nutr Biochem, 2012, 23, 1627-1639). These alterations are not evident at an early age but usually manifest themselves in adulthood. When investigating the possible utility of measuring in blood cells or other easily obtained samples, the levels or concentrations of several thousands of parameters (several thousands of different mRNAs) we discover, surprisingly, that certain combinations of expression levels of gene messenger RNAs concrete (Lrp11 and combinations of this with other genes, those described in Tables 3, 4, 5, 6 and 1), faithfully represented early biomarkers that the developing organism, due to previous malnutrition or other causes, has acquired the propensity to accumulate an excess of fat that could lead to different degrees of overweight or even obesity and other alterations or associated diseases, at different stages of his future life.

Another surprising aspect of the invention refers to the fact that with the methods of the invention it is possible to identify the subjects with high risk of overweight or related complications in adulthood and who are potentially candidates for exclusive breastfeeding or milk feeding of commercial formulation supplemented with leptin during the period of breastfeeding. The authors of the present invention have surprisingly observed that oral supplementation with physiological doses of leptin during lactation is capable of reversing the changes produced in the gene expression profile of PBMCs caused by maternal restriction. By

10 Therefore, the present invention allows the identification of subjects with a high risk of

Being overweight or other complications in adulthood that can prevent or prevent the development of these by exclusive feeding with breastfeeding or with milk supplemented with leptin during the period of breastfeeding.

Table 1. Group of 219 genes used to establish the risk of suffering from obesity or related alterations. In the first place, it is the 22 genes that have altered their genetic expression in a very significant way in subjects who have suffered fetal caloric restriction and who reverse said alteration by oral supplementation with physiological doses of leptin during lactation, along with 196 genes that are altered, with greater significance, their expression after fetal caloric restriction and that partially reverse said alteration after oral supplementation with physiological doses of leptin during lactation. In addition, the IRX3 gene that shows a pattern of similar changes is included, without reaching the threshold of statistical significance of the previous ones, due to its proven biological plausibility related to obesity. They include: Slbolo, being the official abbreviation of the gene; ID, the identification code of the National Center for Biotechnology Information (NCBI) database; Full official name of the gene in Spanish. Also, the significance value (p) and the multiple change values (or fold changes in English, FC) resulting from the statistical analysis of Examples 1 and 2 are also included comparing the CR group with the control group, the CR group -Leptin with the CR group and 20 the CR-Leptin group with the control group.

 Symbol

 CR vs. Control CR-Leptin vs. CR CR-Leptin vs. Control

 P

 FC p FC p FC

 Lrp11

 0.002 0.70 0.001 -0.77 0.690 -0.08

 Gls

 0.008 0.74 0.007 -0.80 0.777 -0.07

 Ubash3b

 0.010 0.45 0.000 -0.65 0.212 -0.20

 Crmp1

 0.004 0.82 0.008 -0.78 0.142 0.04

 Gla

 0.004 0.88 0.004 -0.96 0.770 -0.08

 Paox

 0.008 0.62 0.010 -0.64 0.939 -0.02

 Rnf10

 0.003 -1.22 0.010 1.11 0.777 -0.11

 Selenbp1

 0.001 -0.93 0.007 0.81 0.644 -0.12

 Tmsb4x

 0.010 0.84 0.010 -0.91 0.815 -0.07

 Smagp

 0.000 -0.50 0.006 0.41 0.468 -0.09

 Diexf

 0.002 0.73 0.006 -0.66 0.749 0.07

 Gabra6

 0.002 -1.00 0.004 0.96 0.876 -0.04

 Fycol

 0.003 0.57 0.010 -0.51 0.751 0.06

 Fosos

 0.003 -0.64 0.009 0.60 0.824 -0.04

 Bucsl

 0.004 -0.47 0.004 0.51 0.804 0.04

 Chrnd

 0.006 -0.56 0.004 0.62 0.745 0.06

 Cacnalc

 0.006 -0.65 0.009 0.66 0.960 0.01

 Slc7a5

 0.007 -0.87 0.000 1.20 0.266 0.33

 Myo3b

 0.007 -0.42 0.010 0.43 0.943 0.01

 Myt1

 0.007 -0.57 0.005 0.64 0.730 0.07

 Aloxe3

 0.009 -0.54 0.005 0.63 0.655 0.09

 Grm6

 0.010 -0.66 0.004 0.79 0.561 0.14

 Itgal

 0.000 0.71 0.067 0.31 0.033 -0.40

 Prm1

 0.000 0.56 0.017 0.37 0.241 -0.18

 Pcmtd2

 0.000 0.72 0.018 0.45 0.158 -0.27

 Crtc1

 0.000 -0.89 0.019 -0.53 0.121 0.36

 Olr1075

 0.001 -0.95 0.366 -0.23 0.015 0.72

 Ctla2a

 0.001 0.88 0.243 0.28 0.026 -0.60

 Olr1500

 0.001 0.71 0.012 0.51 0.347 -0.19

 Txnip

 0.001 0.91 0.079 0.46 0.098 -0.46

 Bcap29

 0.001 0.76 0.144 0.32 0.057 -0.45

 Stk4

 0.002 0.74 0.324 0.21 0.023 -0.53

 Myc

 0.002 1.04 0.048 0.61 0.173 -0.43

 Tsc22d3

 0.002 0.86 0.066 0.46 0.138 -0.39

 Msh4

 0.002 -0.61 0.141 -0.26 0.075 0.35

 Zc3h15

 0.002 0.58 0.179 0.23 0.059 -0.35

 Uri1

 0.002 0.95 0.532 0.17 0.014 -0.78

 Il10

 0.002 -0.59 0.042 -0.36 0.224 0.23

 Zfp503

 0.002 -0.52 0.316 -0.15 0.031 0.37

 Ldlrapl

 0.002 0.81 0.258 0.27 0.043 -0.54

 Cirhla

 0.002 0.67 0.183 0.27 0.066 -0.40

 Acp6

 0.002 0.75 0.122 0.35 0.101 -0.40

 Olr1394

 0.002 0.72 0.373 0.19 0.027 -0.53

 Osbplla

 0.002 0.75 0.304 0.23 0.037 -0.52

 Cd2

 0.002 0.78 0.202 0.30 0.062 -0.48

 Bcl2

 0.002 0.96 0.351 0.27 0.031 -0.69

 Meis3

 0.003 0.64 0.198 0.25 0.068 -0.39

 Serpinf2

 0.003 0.48 0.360 0.13 0.032 -0.35

 Pkia

 0.003 0.92 0.286 0.30 0.046 -0.62

 Cd40lg

 0.003 0.99 0.196 0.39 0.072 -0.60

 Slc9a3r1

 0.003 0.51 0.032 0.35 0.335 -0.16

 Bcap31

 0.003 0.71 0.487 0.15 0.024 -0.56

 Prmt3

 0.003 0.74 0.281 0.25 0.052 -0.49

 Ebpl

 0.003 0.77 0.155 0.35 0.106 -0.42

 Cd247

 0.003 0.75 0.096 0.40 0.160 -0.35

 Wash2

 0.003 0.59 0.399 0.15 0.033 -0.43

 Tgm1

 0.003 -0.87 0.024 -0.64 0.432 0.23

 Rps19

 0.003 0.78 0.386 0.21 0.035 -0.57

 Uba5

 0.004 0.91 0.199 0.37 0.084 -0.54

 RT1-EC2

 0.004 1.22 0.088 0.67 0.183 -0.55

 RT1-A3

 0.004 1.06 0.093 0.57 0.176 -0.49

 Mpp5

 0.004 0.73 0.411 0.19 0.035 -0.54

 Pla2g12a

 0.004 0.77 0.358 0.22 0.042 -0.54

 Glt1d1

 0.004 -0.71 0.536 -0.14 0.023 0.57

 Stau2

 0.004 0.77 0.608 0.12 0.019 -0.65

 Olr1602

 0.004 -0.71 0.055 -0.45 0.274 0.26

 Mtss1

 0.004 0.62 0.238 0.23 0.073 -0.39

 Vapb

 0.004 0.51 0.805 0.04 0.011 -0.47

 Ppp1r12c

 0.004 0.49 0.400 0.13 0.039 -0.36

 Pacsl

 0.004 0.60 0.175 0.26 0.105 -0.34

 Calr

 0.004 -0.64 0.490 -0.14 0.029 0.50

 Txlng

 0.004 0.63 0.722 0.07 0.015 -0.56

 Satbl

 0.004 0.90 0.176 0.40 0.121 -0.50

 P4ha2

 0.004 -0.79 0.022 -0.62 0.520 0.18

 Olr239

 0.005 -0.52 0.020 -0.42 0.577 0.11

 Ifi44l

 0.005 1.01 0.223 0.40 0.089 -0.61

 Serpinb6b

 0.005 0.86 0.268 0.31 0.072 -0.55

 Dhx32

 0.005 0.49 0.714 0.06 0.016 -0.44

 Ddx50

 0.005 0.61 0.367 0.18 0.049 -0.43

 Zpbp2

 0.005 0.60 0.253 0.22 0.079 -0.38

 Arl5a

 0.005 0.55 0.202 0.23 0.103 -0.32

 Amotl2

 0.005 -0.61 0.356 -0.18 0.052 0.43

 Cyth1

 0.005 0.70 0.186 0.30 0.121 -0.39

 Nap1l1

 0.005 0.68 0.628 0.11 0.022 -0.57

 Pfkp

 0.005 0.62 0.241 0.24 0.087 -0.38

 The t

 0.005 0.96 0.266 0.35 0.078 -0.61

 Npr1

 0.005 -0.40 0.012 -0.35 0.735 0.05

 Hpse

 0.005 0.82 0.484 0.19 0.036 -0.63

 Slc16a8

 0.005 -0.51 0.267 -0.19 0.081 0.32

 Ncor1

 0.005 0.54 0.629 0.09 0.024 -0.45

 Dmrtc1a

 0.005 -0.75 0.481 -0.17 0.037 0.58

 Avil

 0.005 -0.55 0.565 -0.10 0.029 0.45

 Lcmt1

 0.005 0.58 0.149 0.28 0.151 -0.30

 Friend1

 0.005 0.87 0.336 0.28 0.062 -0.59

 Cd99l2

 0.005 0.95 0.132 0.48 0.177 -0.47

 Fcar

 0.006 -0.84 0.110 -0.45 0.200 0.39

 Il15

 0.006 0.65 0.171 0.30 0.135 -0.35

 Prtn3

 0.006 -0.69 0.657 -0.10 0.023 0.59

 Olr107

 0.006 -0.64 0.490 -0.15 0.037 0.50

 Cnga1

 0.006 0.72 0.168 0.33 0.138 -0.39

 Eef2

 0.006 0.58 0.633 0.09 0.024 -0.49

 Zfp638

 0.006 0.45 0.722 0.05 0.019 -0.40

 B3gnt8

 0.006 -0.61 0.614 -0.10 0.026 0.50

 Prpsapl

 0.006 0.57 0.833 0.04 0.014 -0.53

 Panxl

 0.006 0.59 0.855 0.04 0.013 -0.55

 Wdr77

 0.006 0.63 0.199 0.27 0.119 -0.36

 Gnl1

 0.006 0.60 0.529 0.13 0.034 -0.47

 Abat

 0.006 0.69 0.159 0.33 0.155 -0.36

 Spo11

 0.006 0.62 0.234 0.25 0.101 -0.37

 Cd38

 0.006 0.81 0.314 0.27 0.072 -0.54

 Trmt11

 0.006 0.55 0.436 0.14 0.046 -0.41

 Pgrmc1

 0.006 0.80 0.592 0.14 0.029 -0.66

 Gar1

 0.006 0.78 0.716 0.09 0.021 -0.69

 Nphs1

 0.006 -0.68 0.118 -0.36 0.202 0.31

 Olr500

 0.006 0.58 0.032 0.44 0.493 -0.14

 Rasa4

 0.006 0.53 0.098 0.30 0.241 -0.23

 Ets1

 0.006 1.05 0.163 0.50 0.154 -0.55

 Arhgef1

 0.006 0.63 0.223 0.25 0.103 -0.38

 Steap4

 0.006 -0.51 0.214 -0.22 0.118 0.29

 Nt5c3l

 0.006 0.76 0.084 0.46 0.272 -0.30

 Rps11

 0.006 0.75 0.569 0.14 0.033 -0.61

 Ftsjd1

 0.007 0.54 0.666 0.08 0.025 -0.46

 Gstp1

 0.007 0.59 0.477 0.14 0.044 -0.45

 Ppp1r9a

 0.007 -0.60 0.287 -0.22 0.088 0.38

 Faah

 0.007 0.79 0.137 0.41 0.187 -0.39

 Stat4

 0.007 0.80 0.113 0.44 0.225 -0.36

 Lef1

 0.007 0.89 0.114 0.49 0.223 -0.40

 Rgs1

 0.007 1.73 0.333 0.58 0.076 -1.16

 Slc34a3

 0.007 0.59 0.062 0.39 0.352 -0.20

 Pdcd4

 0.007 0.59 0.309 0.21 0.084 -0.39

 Prkcq

 0.007 0.95 0.274 0.36 0.097 -0.59

 Paqr5

 0.007 0.97 0.177 0.46 0.154 -0.51

 Cmtm3

 0.007 0.53 0.206 0.23 0.133 -0.30

 Chorus 2b

 0.007 0.42 0.065 0.28 0.344 -0.15

 Icos

 0.007 0.70 0.435 0.19 0.054 -0.52

 Bmp8a

 0.007 -0.90 0.464 -0.23 0.049 0.67

 Zfp259

 0.007 0.47 0.220 0.20 0.125 -0.27

 Kcnmb4

 0.007 0.81 0.190 0.37 0.166 -0.44

 Nipall

 0.007 0.52 0.254 0.20 0.107 -0.31

 Pigl

 0.007 0.62 0.445 0.16 0.053 -0.46

 Zfp709

 0.007 0.51 0.234 0.21 0.119 -0.30

 Commd7

 0.008 0.63 0.192 0.29 0.149 -0.34

 Tspan6

 0.008 0.53 0.299 0.20 0.101 -0.33

 Chpt1

 0.008 0.67 0.763 0.07 0.022 -0.60

 Ywhaz

 0.008 0.62 0.822 0.05 0.019 -0.57

 Ret

 0.008 0.90 0.173 0.43 0.168 -0.47

 Gipc3

 0.008 -0.83 0.355 -0.27 0.076 0.57

 Rbm3

 0.008 0.46 0.175 0.22 0.173 -0.24

 Tcf12

 0.008 0.80 0.649 0.13 0.031 -0.67

 St8sia1

 0.008 0.91 0.472 0.23 0.053 -0.68

 Nlk

 0.008 0.57 0.884 0.03 0.017 -0.54

 Smyd2

 0.008 0.70 0.191 0.32 0.156 -0.38

 Plcg1

 0.008 0.57 0.159 0.29 0.186 -0.29

 Ctnnal1

 0.008 0.66 0.426 0.18 0.062 -0.47

 Dnmt3a

 0.008 0.73 0.366 0.23 0.076 -0.50

 Stk33

 0.008 -0.69 0.322 -0.24 0.090 0.45

 Mpzl1

 0.008 -0.53 0.249 -0.22 0.121 0.32

 Noc2l

 0.008 0.61 0.646 0.10 0.033 -0.52

 Olr1481

 0.008 -0.43 0.194 -0.20 0.158 0.23

 Aph1a

 0.008 -0.43 0.429 -0.12 0.063 0.31

 Dyrk2

 0.008 0.65 0.195 0.30 0.158 -0.35

 Pglyrp4

 0.008 -0.60 0.354 -0.19 0.082 0.40

 Cd2ap

 0.008 0.57 0.639 0.09 0.034 -0.47

 Il7r

 0.008 0.84 0.594 0.16 0.039 -0.69

 Shprh

 0.008 0.55 0.096 0.33 0.292 -0.22

 Tgm6

 0.009 -0.49 0.528 -0.11 0.047 0.38

 Hpcall

 0.009 0.45 0.331 0.16 0.090 -0.30

 Itk

 0.009 1.07 0.143 0.56 0.213 -0.51

 Evl

 0.009 0.92 0.355 0.30 0.083 -0.62

 Pafah1b3

 0.009 0.54 0.366 0.17 0.080 -0.37

 Cdh19

 0.009 -0.82 0.204 -0.37 0.154 0.45

 Plscr2

 0.009 0.53 0.941 0.01 0.016 -0.52

 Scnnlb

 0.009 0.49 0.242 0.20 0.111 -0.28

 Unc13d

 0.009 0.54 0.688 0.08 0.033 -0.45

 Ctsw

 0.009 0.72 0.218 0.32 0.147 -0.40

 Nob1

 0.009 0.55 0.526 0.12 0.048 -0.43

 Pstk

 0.009 0.59 0.359 0.19 0.083 -0.40

 Upf3b

 0.009 0.46 0.354 0.15 0.085 -0.31

 Tsr2

 0.009 0.61 0.380 0.19 0.078 -0.42

 C1galt1

 0.009 0.69 0.428 0.19 0.066 -0.49

 Rnf125

 0.009 0.94 0.216 0.42 0.125 -0.52

 Olr439

 0.009 0.74 0.722 0.09 0.028 -0.64

 Csnk1g2

 0.009 0.56 0.373 0.18 0.081 -0.38

 Kdm6b

 0.009 -0.48 0.502 -0.12 0.055 0.37

 Camk4

 0.009 0.81 0.539 0.18 0.049 -0.63

 Muc5b

 0.009 -0.93 0.794 -0.09 0.024 0.84

 Camp

 0.009 -0.54 0.273 -0.21 0.121 0.33

 Axin2

 0.009 0.65 0.234 0.28 0.143 -0.37

 Churc1

 0.009 -0.52 0.099 -0.31 0.306 0.20

 Ptpn9

 0.009 0.48 0.639 0.08 0.037 -0.40

 Zap70

 0.009 1.08 0.234 0.47 0.144 -0.62

 Slc18a2

 0.010 0.72 0.275 0.28 0.122 -0.44

 Kcnq4

 0.010 -0.69 0.022 -0.60 0.724 0.09

 Tbx3

 0.010 -0.52 0.309 -0.19 0.107 0.33

 Oxsm

 0.010 0.50 0.263 0.20 0.129 -0.30

 Phemx

 0.010 0.60 0.501 0.15 0.057 -0.46

 Mx1

 0.010 0.89 0.146 0.47 0.227 -0.42

 Znhit6

 0.010 0.69 0.432 0.20 0.070 -0.50

 RGD1559724

 0.010 0.75 0.406 0.22 0.077 -0.53

 RGD1564300

 0.010 0.70 0.533 0.16 0.052 -0.54

 Dgka

 0.010 0.92 0.205 0.42 0.168 -0.49

 Elane

 0.010 -0.60 0.355 -0.20 0.092 0.40

 Slc9a9

 0.010 0.56 0.331 0.20 0.100 -0.36

 Ireb2

 0.010 0.66 0.843 0.05 0.022 -0.61

 Tcrb

 0.010 0.77 0.152 0.40 0.222 -0.36

 Skapl

 0.010 0.94 0.195 0.44 0.178 -0.50

 I ca

 0.010 0.57 0.352 0.19 0.094 -0.38

 Adsl

 0.010 0.48 0.368 0.16 0.090 -0.33

 Slc12a7

 0.010 0.56 0.349 0.19 0.096 -0.37

 Gnpnatl

 0.010 0.60 0.488 0.15 0.062 -0.45

 Sirt5

 0.010 0.60 0.496 0.15 0.060 -0.45

 Il21r

 0.010 0.78 0.208 0.36 0.177 -0.42

 Gdi1

 0.010 0.47 0.689 0.07 0.035 -0.40

 Eif3e

 0.010 0.56 0.606 0.10 0.044 -0.45

 Nol9

 0.010 0.54 0.478 0.14 0.064 -0.40

 Gart

 0.010 0.48 0.467 0.13 0.067 -0.35

 Mthfr

 0.010 -0.57 0.399 -0.18 0.086 0.39

 Isca1

 0.010 -0.74 0.917 -0.03 0.020 0.71

 IRX3

 0.069 0.26 0.497 -0.10 0.254 0.16

Table 2. List of the 224 genes that underwent changes in the profile of genetic expression in PBMCs of 25-day rats as a result of maternal caloric restriction during gestation. In addition, the Irx3 gene is included, which shows a pattern of similar changes, without reaching the threshold of statistical significance of the previous ones, due to its proven biological plausibility related to obesity. ID, the identification code of the National Center for Biotechnology Information (NCBI) database; Official and full name of the gene in Spanish, and the biological process in which the gene of interest is involved.

 Symbol

 ID Name Biological process

 Lrp11

 NM_001106217 Protelna related to the Metabolism receptor (lipids)

 Symbol

 ID Name Biological process

 low density lipoprotelnas 11

 Gls

 NM 001109968 Glutaminase Metabolism (protelnas / polyamines)

 Ubash3b

 NM_001191792 Contains a domain associated with ubiquitin and SH3, B Metabolism (protelnas / polyamines)

 Crmpl

 NM_012932 Protelna mediating the response to collapsin 1 Nervous system

 Gla

 NM_001108820 Galactosidase, alpha Metabolism (carbohydrates)

 Paox

 NM_001106311 Polyamine oxidase Metabolism (proteins / polyamines)

 Rnf10

 NM_001011904 Zinc finger protelna type RING 10 Nervous system

 Selenbpl

 NM_080892 Selenium binding protein 1 Cellular replacement

 Tmsb4x

 NM 031136 Thymosin beta 4, linked to X Cytoskeleton

 Smagp

 NM_182817 Small cell adhesion glucoproteln Cell communication

 Diexf

 NM_001013986 Homologous to the digestive organ expansion factor (zebrafish) Cell turnover

 Gabra6

 NM_021841 Gamma-aminobutyric acid receptor (GABA), alpha 6 Nerve signaling

 Fyco1

 NM_001106870 Contains a FYVE and spiral coil domain 1 Transport

 Fos1

 NM 012953 Analog antigen to fos 1 Cellular replacement

 Bucs1

 NM_001108502 Butyryl coenzyme A synthetase 1 Metabolism (lipids)

 Chrnd

 NM 019298 Cholinergic receptor, nicotlnic, delta Nerve signaling

 Cacna1c

 ENSRNOT000000093 43 Voltage-dependent calcium channel, type L, subunit 1C Signaling

 Slc7a5

 NM_017353 Family solute transporter 7 (Light chain amino acid transporter, system L) member 5 Transport

 Myo3b

 NM_001191901 Myosin IIIB Cytoskeleton

 Myt1

 NM_001108615 Myelin transcription factor 1 Nervous system

 Aloxe3

 NM_001105793 Araquinodato lipoxygenase 3 Metabolism (lipids)

 Grm6

 NM_022920 Glutamate receptor, metabotrophic 6 Nerve signaling

 Itgal

 NM_001033998 Integrina alfa L Machinery

 Symbol

 ID Name Biological process

 transcriptional / translational

 Prm1

 NM 001002850 Protamine 1 Metabolism (protelnas / polyamines)

 Pcmtd2

 NM_001107810 Contains a domain of the protein L-isoaspartate (D-aspartate) O-methyltransferase 2 Cellular communication

 Crtcl

 NM_001047115 CREB-regulated transcription coactivator 1 Cellular replacement

 Olr1075

 NM_001000421 Olfactory receptor 1075 Immune system

 Ctla2a

 NM_001109115 Protelna associated with cytotoxic T lymphocytes 2 alpha Transport

 Olr1500

 NM_001000942 Olfactory receptor 1500 Metabolism (central)

 Txnip

 NM 001008767 Protelna that interacts with thioredoxin Sensory perception

 Bcap29

 NM_001006980 Protelna associated with the B cell receptor, 29 Sensory perception

 Stk4

 NM 001107800 Serine / threonine kinase 4 Metabolism (lipids)

 Myc

 NM_012603 Oncogene of myelocytomatosis Cell turnover

 Tsc22d3

 NM_031345 TSC22 domain family, member 3 Transcriptional / translational machinery

 Msh4

 NM_001106477 MutS homologo 4 (from E. coli) Transcriptional / translational machinery

 Zc3h15

 NM_001010963 Contains zinc finger type CCCH 15 Transport (kidney)

 Uri1

 NM_001107507 URI1, chaperone analogous to prefoldin Metabolism (lipids)

 Il10

 NM_012854 Interleukin 10 Immune system

 Zfp503

 NM_001107250 Zinc finger protelna 503 Immune system

 Ldlrap1

 NM 001109271 Protelna adapter for low density lipoproteln receptor 1 Cellular replacement (cell cicle)

 Cirh1a

 NM_001009640 Cirrhosis, autosomal recessive 1A Cellular replacement

 Acp6

 NM 001031645 Phosphatase acid 6, lysophosphatic metabolism (lipids)

 Olr1394

 NM 001001091 Olfactory receiver 1394 Transcriptional / translational machinery

 Osbpl1a

 NM_172023 Analog to oxysterol binding protein 1A Sensory perception

 Symbol

 ID Name Biological process

 Cd2

 NM_012830 Molecula Cd2 Senalization

 Bcl2

 NM 016993 Cell B CLL / lymphoma 2 Metabolism (protelnas / polyamines)

 Meis3

 NM 001108472 Meis homeobox 3 Metabolism (lipids)

 Serpinf2

 NM_001011892 Serpine peptidase inhibitor, subtype F (alpha-2 antiplasmin, pigment epithelial derived factor), member 2 Cytoskeleton

 Pkia

 FQ211701 Alpha protelna kinase inhibitor (cAMP dependent, catalltica) Senalization

 Cd40lg

 NM_053353 Ligand CD40 Blood

 Slc9a3r1

 NM 021594 Family 9 solute transporter (sodium / hydrogen exchanger), member 3 regulator 1 Immune system

 Bcap31

 NM 001004224 Protelna associated with the B cell receptor, 31 Transcriptional / translational machinery

 Prmt3

 NM_053557 Protelna arginine methyltransferase 3 Immune system

 Ebpl

 NM 001108381 Analog to the binding protein to the emopamil Metabolism (protelnas / polyamines)

 Cd247

 NM_170789 Molecula Cd247 Immune system

 Wash2

 NM 001127390 Homologue 2 of the WAS family of proteins Transcriptional / translational machinery

 Tgm1

 NM_031659 Transglutaminase 1, polypeptide K Metabolism (protelnas / polyamines)

 Rps19

 NM_001037346 Protelna ribosomal S19 Cytoskeleton

 Uba5

 NM 001009669 Activating enzyme of the ubiquitin 5 modifier Metabolism (protelnas / polyamines)

 RT1-EC2

 M10094 RT1 lb class, EC2 locus Immune system

 RT1-A3

 NM_001008830 RT1 class l, locus A3 Immune system

 Mpp5

 NM_001108034 Membrane prothena, palmitoylated 5 (member 5 of the subfamily MAGUK p55) Nervous system

 Pla2g12a

 NM 001108565 Phospholipase A2, group XIIA Metabolism (lipids)

 Glt1d1

 ENSRNOT000000645 26 Contains a glucosyltransferase 1 domain Metabolism (carbohydrates)

 Stau2

 NM 001007149 Staufen homologue 2, RNA binding protein (Drosophila) Nervous system

 Olr1602

 NM_001000909 Olfactory receptor 1602 Sensory perception

 Symbol

 ID Name Biological process

 Mtssl

 NM_001130563 Metastasis suppressor 1 Cellular replacement

 Vapb

 NM_021847 Protelna B and C associated with VAMP (membrane associated with vesicles) Transport

 Ppp1r12c

 NM_001191946 Protelna phosphatase 1, regulatory subunit 12C Cytoskeleton

 Pacsl

 NM 134406 Protelna 1 involved in the arrangement of the acid phosphoforin assembly Transport

 Calr

 NM 022399 Calreticulin Metabolism (protelnas / polyamines)

 Txlng

 ENSRNOT000000068 43 Gamma Taxiline Cell replacement

 Satbl

 NM_001012129 SATB homeobox 1 Transcriptional / translational machinery

 P4ha2

 NM_001108275 Prolil 4-hydroxylase, alpha II polypeptide Metabolism (central)

 Olr239

 NM_001000211 Olfactory receptor 239 Sensory perception

 Ifi44l

 XM_227820 Interferon 44 Analog Induced by Interferon Immune System

 Serpinb6 b

 NM_001012214 Serine peptidase inhibitor (or cystel), subtype B, member 6b Metabolism (protelnas / polyamines)

 Dhx32

 NM 001130039 DEAH polypeptide (Asp-Glu-Ala-His) 32 Transcriptional / translational machinery

 Ddx50

 NM_001013198 DEAH polypeptide (Asp-Glu-Ala-Asp) 50 Transcriptional / translational machinery

 Zpbp2

 NM 001007011 Protelna of union to the zona pelcida 2 Others

 Arl5a

 ENSRNOT000000091 81 Analog to ADP 5A ribosylation factor Others

 Amotl2

 NM_031717 Angiomyotin Analog 2 Other

 Cyth1

 NM_053910 Cytohesin 1 Transport

 Nap1l1

 NM_053561 Analog to the nucleosome assembly block 1 Cellular replacement

 Pfkp

 L25387 Phosphofructokinase, platelet Metabolism (carbohydrates)

 The t

 NM_030853 Binder for activation of T cells Immune system

 Npr1

 NM 012613 Natriuretic peptide receptor A / guanylate cyclase A (atrionatriuretic peptide receptor A) Senalization

 Symbol

 ID Name Biological process

 Hpse

 NM_022605 Heparanase Metabolism (carbohydrates)

 Slc16a8

 NM_031744 Family 16 solute transporter, member 8 (Carboxylic acid transporter 3) Transportation

 Ncorl

 XM_001077495 Nuclear receiver correpressor 1 Transcriptional / translational machinery

 Dmrtcla

 NM_001025288 C1A family analogous to DMRT Transcriptional / translational machinery

 Avil

 NM_024401 Advilina Cytoskeleton

 Lcmtl

 NM_199405 Leucine carboxymethyltransferase 1 Metabolism (protelnas / polyamines)

 Friend1

 BC167749 Adhesion Molecule 1 with Ig type domain Nervous system

 Cd99l2

 NM_134459 Analog to the CD99 molecule 2 Cellular communication

 Fcar

 NM_201992 Fc IgA receptor Immune system

 Il15

 NM 013129 Interleukin 15 Immune system

 Prtn3

 NM_001024264 Proteinase 3 Metabolism (protelnas / polyamines)

 Olr107

 NM 001000148 Olfactory receptor 107 Sensory perception

 Cnga1

 NM_053497 Alpha 1 nucleicide dependent channel 1 Sensory perception

 Eef2

 NM_017245 Elongation factor of eukaryotic translation 2 Transcriptional / translational machinery

 Zfp638

 NM 001107868 Zinc finger protelna 638 Transcriptional / translational machinery

 B3gnt8

 NM_001107492 UDP-GlcNAc: betaGal beta- 1,3-N- acetylglucosaminyltransfera sa 9 Metabolism (protelnas / polyamines)

 Prpsap1

 NM 022545 Protelna associated with phosphoribosyl pyrophosphate synthetase 1 Metabolism (nucleotides)

 Panx1

 NM_199397 Pannexin 1 Cellular communication

 Wdr77

 NM_001008771 Repeated domain WD 77 Transcriptional / translational machinery

 Gnl1

 NM 212500 Analog to guanine nucleotide binding protein Immune system

 Abat

 NM_031003 4-aminobutyrate aminotransferase Nerve signaling

 Symbol

 ID Name Biological process

 Spoil

 NM_001108964 Homologue of the SPO11 meiotic prothena covalently linked to DSB (S. cerevisiae) Others

 Cd38

 NM_013127 Molecula CD38 Senalization

 Trmtil

 ENSRNOT000000194 36 Homologue of tRNA methyltransferase 11 (S. cerevisiae) Transcriptional / translational machinery

 Pgrmcl

 NM_021766 Progesterone receptor membrane component 1 Nervous system

 Garl

 NM 001024306 Homologue of the GAR1 ribonucleoproteln (yeast)

 Nphsi

 NM_022628 Nephrosis 1, congenital, Finnish type Other

 Olr500

 NM 001000680 Olfactory receptor 500 Sensory Perception

 Rasa4

 XM_002724808 Activator 4 of protelna p21 RAS Senalization

 Ets1

 L20681 Homologous 1 of the E26 erytoblastosis v-ets oncogene cell turnover

 Arhgef1

 NM_021694 Rho factor guanine nucleotide exchanger (GEF) 1 Transcriptional / translational machinery

 Steap4

 NM_001044265 Member 4 of the STEAP family Metabolism (central)

 Nt5c3l

 NM_001007723 5'-nucleotidase, cytosolic type-III Metabolism (nucleotides)

 Rps11

 NM 031110 Protelna ribosomal S11 Transcriptional / translational machinery

 Ftsjd1

 NM 001106186 Contains the FtsJ domain of methyltransferase 1 Transcriptional / translational machinery

 Gstp1

 NM_012577 Glutathione S-transferase pi 2 Others

 Ppp1r9a

 NM 053473 Protelna phosphatase 1, regulatory subunit 9A Nerve signaling

 Faah

 NM_024132 Fatty acid amide hydrolase Metabolism (lipids)

 Stat4

 NM_001012226 Signal transducer and transcription activator 4 Senalization

 Lef1

 NM_130429 Binding factor 1 to lymphoid enhancer Cellular replacement

 Rgs1

 NM_019336 Regulator 1 of signaling by protelna G Senalization

 Slc34a3

 NM 139338 Family 34 solute transporter (Transport phosphate

 Symbol

 ID Name Biological process

 sodium), member 3

 Pdcd4

 NM 022265 Programmed cell death 4 Cellular replacement

 Prkcq

 ENSRNOT000000259 01 Protelna quinsa C, tit Senalization

 Paqr5

 NM_001014092 Member V of the family of progestin and adiponectin receptors Senalization

 Cmtm3

 NM 001106164 Protelna 3 containing a transmembrane domain MARVEL analogous to CKLF Cellular communication

 Chorus 2b

 ENSRNOT000000209 51 Coronina, actin-binding protein, 2B Cytoskeleton

 Icos

 NM_022610 T-cell inducible co-stimulator Immune system

 Bmp8a

 NM_001109432 Morphogenic bone protein 8a Cell turnover

 Zfp259

 NM_001137646 Zinc finger protelna 259 Cellular replacement

 Kcnmb4

 NM_023960 High-conductance calcium channel activated by calcium, subfamily M, beta member 4 Transport

 Nipal1

 NM 001106003 Contains an analog domain to NIPA 1 Transport

 Pigl

 ENSRNOT000000041 13 Phosphatidylinositol glycan anchor biosynthesis, class L Metabolism (lipids)

 Zfp709

 NM_153731 Zinc finger protelna 709 Transcriptional / translational machinery

 Commd7

 NM_001030029 Contains a COMM 7 domain Senalization

 Tspan6

 NM_001100672 Tetraspanin 6 Senalization

 Chpt1

 NM 001007750 Choline phosphotransferase 1 Metabolism (lipids)

 Ywhaz

 NM_013011 Tyrosine activation protein 3- monooxygenase / tryptophan 5-monooxygenase, zeta polypeptide Senation

 Ret

 NM_001110099 Proto-oncogen ret Senalization

 Gipc3

 NM_001109282 Member 3 of the GIPC family that contains the PDZ domain Cellular replacement

 Rbm3

 NM_053696 Reason for binding to RNA (RNP1, RRM) protelna 3 Transcriptional / translational machinery

 Tcf12

 NM 013176 Transcription factor 12 Transcriptional machinery /

 Symbol

 ID Name Biological process

 translational

 St8sia1

 NM_012813 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 Metabolism (lipids)

 Nlk

 NM_001191924 Analog kinase at nemo Senalization

 Smyd2

 NM_206851 Contains a MYND and SET 2 domain Epigenetic modifications

 Plcgl

 NM_013187 Phospholipase C, gamma 1 Senalization

 Ctnnall

 NM_001106649 Catenin (prothine associated with cadherin), alpha 1 analogue Cellular communication

 Dnmt3a

 NM 001003958 DNA (cytosine-5 -) - methyltransferase 3 alpha Epigenetic modifications

 Stk33

 ENSRNOT000000195 97 Serine / threonine kinase 33 Cytoskeleton

 Mpzll

 NM_001007728 Analog to myelin zero protein 1 Senalization

 Noc2l

 NM_001033897 Homologous of the associated nucleolar complex 2 (S. Cerevisiae) Transcriptional / translational machinery

 Olr1481

 NM 001000527 Olfactory receptor 1481 Sensory perception

 Aph1a

 NM 001014255 Homologue A previous defective farlnge 1 (C. Cerevisiae) Metabolism (protelnas / polyamines)

 Dyrk2

 NM_001108100 Phosphorylation-regulated dual specific tyrosine kinase Cell turnover

 Pglyrp4

 NM_001191708 Peptidoglycan recognition protein 4 Immune system

 Cd2ap

 NM_181475 Protelna associated with CD2 Cytoskeleton

 Il7r

 NM 001106418 Interlequin receiver 7 Senalization

 Shprh

 NM 001107470 Helicase SNF2 with PHD domain and RING histone linker Cell turnover

 Tgm6

 ENSRNOT000000090 97 Transglutaminase 6 Metabolism (protelnas / polyamines)

 Hpcal1

 NM_017356 Analog to hypocalcin 1 Nerve signaling

 Itk

 NM_001108825 IL2 inducible T cell kinase Immune system

 Evl

 NM_024147 Analog to Enah / Vasp Cytoskeleton

 Pafah1b3

 NM_053654 Platelet activating factor acetylhydrolase, isoform 1b, subunit 3 Nervous system

 Cdh19

 NM_001009448 Cadherina 19, type 2 Cellular communication

 Plscr2

 NM 001014094 Phospholipid Scramblase 2 Blood

 Scnn1b

 NM_012648 Sodium channel, not Transport

 Symbol

 ID Name Biological process

 voltage dependent, beta

 Unc13d

 NM 138844 Homologue D of UNC-13 (C. elegans) Immune system

 Ctsw

 NM_001024242 Cathepsin W Metabolism (protelnas / polyamines)

 Nob1

 NM_199086 Homologue 1 of the NIN1 / RPN12 union (S. cerevisiae) Transcriptional / translational machinery

 Pstk

 ENSRNOT000000279 67 Similar to phosphoseril-tRNA kinase Transcriptional / translational machinery

 Upf3b

 NM_001135873 Homologue B of the UPF3 regulator of antisense transcripts (yeast) Transcriptional / translational machinery

 Tsr2

 NM 001115027 TSR2 homologue, of accumulation of ARNr 20S (S. cerevisiae) Transcriptional / translational machinery

 Clgaltl

 NM_022950 Central synthase 1, glycoproteln-N-acetylgalactosamine 3-beta-galactosyltransferase, 1 Metabolism (protelns / polyamines)

 Rnf125

 NM 001108424 Zinc finger protelna 125 Metabolism (protelnas / polyamines)

 Olr439

 NM_001000281 Olfactory receptor 439 Sensory perception

 Csnk1g2

 NM_023102 Caselna kinase 1, gamma 2 Metabolism (protelnas / polyamines)

 Kdm6b

 NM_001108829 Specific lysine demethylase 6B Epigenetic modifications

 Camk4

 NM 012727 Protelna kinase IV dependent on calcium / calmodulin Senalization

 Muc5b

 ENSRNOT000000289 67 Mucina 5B oligomerica, gel former in mucus Other

 Camp

 CB577971 Cathelicidin Antimicrobial Peptide Immune System

 Axin2

 NM_024355 Axina 2 Senalization

 Churc1

 NM_001106741 Protelna containing the churchill domain Nervous system

 Ptpn9

 NM 001013040 Protelna tyrosine phosphatase non-receptor type 9 Blood

 Zap70

 NM_001012002 Protelna kinase associated with the zeta chain (TCR) Immune system

 Slc18a2

 NM_013031 Family 18 solute transporter (vesicular monoamine), member 2 Transportation

 Kcnq4

 AF249748 Voltage dependent potassium channel, Nerve signaling

 Symbol

 ID Name Biological process

 KQT similar subfamily, member 4

 Tbx3

 NM_181638 Box T 3 Transcriptional / translational machinery

 Oxsm

 NM_001100508 3-oxoacil-ACP synthase, mitochondrial Metabolism (lipids)

 Phemx

 XM_002725757 Pan-hematopoietic Blood Expression

 Mx1

 NM_173096 Resistance to myxovirus (influenza virus) 1 Immune system

 Znhit6

 NM 001106203 Que contine zinc finger type-HIT 6 Transcriptional / translational machinery

 RGD155 9724

 ENSRNOT000000478 82 Similar to the ribosomal block 40S S19 Transcriptional / translational machinery

 RGD156 4300

 BC168162 Similar to phosphoseryl-tRNA kinase Transcriptional / translational machinery

 Dgka

 NM 080787 Diacylglycerol kinase, alpha Senalization

 Elane

 NM_001106767 Elastase, expressed in neutrophils Blood

 Slc9a9

 XM_001064905 Family 9 solute transporter (sodium / hydrogen exchanger), isoform 9 Transport

 Ireb2

 NM_022863 Iron-binding element protelna 2 Metabolism (central)

 Tcrb

 BC091428 T cell receptor beta chain Immune system

 Skap1

 NM_173311 Fosfoprotelna 1 associated to the kinase src immune system

 I ca

 NM_001107514 Homologue of the headcase (Drosophila) Cellular replacement

 Adsl

 NM_001130503 Adenylosuccinate lyase Metabolism (nucleotides)

 Slc12a7

 NM 001013144 Family solute transporter 12 (Potassium / chloride transporters), member 7 Transport

 Gnpnat1

 NM_001134757 Glucosamine-phosphate N-acetyltransferase 1 Metabolism (carbohydrates)

 Sirt5

 NM 001004256 Sirtuin 5 Epigenetic modifications

 Il21r

 NM_001012469 Interlequin receiver 21 Senalization

 Gdi1

 NM_017088 GDP dissociation inhibitor 1 Senalization

 Symbol

 ID Name Biological process

 Eif3e

 NM 001011990 Factor 3 of initiation of eukaryotic translation, subunit E Transcriptional / translational machinery

 Nol9

 ENSRNOT000000135 35 Protelna nucleolar 9 Transcriptional / translational machinery

 Gart

 BC087644 Phosphoribosylglycinamide formyltransferase Metabolism (nucleotides)

 Mthfr

 ENSRN0T000000113 84 Methyleneotetrahydrofolate reductase (NAD (P) H) Metabolism (central)

 Isca1

 NM 181626 Homologue to the iron-sulfur center scaffolding site 1 (S. cerevisiae) Metabolism (central)

 Irx3

 NM_001107413 Iroquois homeobox 3 Nervous system (neural development)

 Defa24

 NM_001013053 Defensin, alpha, 24 Immune system

 Cmya5

 XM_001068814 Associated with cardiomyopathy 5 Immune system

 Trim23

 NM 001100637 Contains tripartite motive 23 Metabolism (protelnas / polyamines)

 Dsg2

 XM_001054396 Desmoglelna 2 Cellular replacement

 Tph2

 NM_173839 Tryptophan hydroxylase 2 Nerve signaling

 Slpi

 NM 053372 Leukocyte secretion peptidase inhibitor Immune system

Table 3. Group of 3 genes used to establish the risk of obesity or related alterations. They include: Slbolo, being the official abbreviation of the gene; ID, the identification code of the National Center for 5 Biotechnology Information (NCBI) database; Full official name of the gene in Spanish.

 Symbol

 ID Name

 Lrp11

 NM_001106217 Protelna related to the low density lipoproteln receptor 11

 Gls

 NM_001109968 Glutaminase

 Ubash3b

 NM 001191792 Contains a domain associated with ubiquitin and SH3, B

Table 4. Group of 9 genes used to establish the risk of obesity or related alterations. They include: Slbolo, being the official abbreviation of the gene; ID, the identification code of the National Center for 10 Biotechnology Information (NCBI) database; Full official name of the gene in Spanish.

 Symbol

 ID Name

 Lrp11

 NM_001106217 Protelna related to the low density lipoproteln receptor 11

 Gls

 NM 001109968 Glutaminase

 Ubash3b

 NM_001191792 Contains a domain associated with ubiquitin and SH3, B

 Crmpl

 NM 012932 Protelna mediating the response to collapsin 1

 Gla

 NM 001108820 Galactosidase, alpha

 Paox

 NM_001106311 Polyamine oxidase

 Rnf10

 NM_001011904 RING 10 zinc finger protelna

 Selenbpl

 NM 080892 Prolinena of union to the selenium 1

 Tmsb4x

 NM 031136 Thymosin beta 4, linked to X

Table 5. Group of 22 genes used to establish the risk of obesity or related alterations. They include: Slbolo, being the official abbreviation of the gene; ID, the identification code of the National Center for 5 Biotechnology Information (NCBI) database; Full official name of the gene in Spanish.

 Slbolo

 ID Name

 Lrp11

 NM_001106217 Protelna related to the low density lipoproteln receptor 11

 Gls

 NM_001109968 Glutaminase

 Ubash3b

 NM 001191792 Contains a domain associated with ubiquitin and SH3, B

 Crmp1

 NM_012932 Protelna mediating the response to collapsin 1

 Gla

 NM_001108820 Galactosidase, alpha

 Paox

 NM_001106311 Polyamine oxidase

 Rnf10

 NM_001011904 RING 10 zinc finger protelna

 Selenbp1

 NM_080892 Protelna of union to selenium 1

 Tmsb4x

 NM_031136 Thymosin beta 4, linked to X

 Smagp

 NM 182817 Small cell adhesion glucoproteln

 Diexf

 NM_001013986 Homologue to the expansion factor of the digestive organ (zebrafish)

 Gabra6

 NM 021841 Gamma-aminobutyric acid receptor (GABA), alpha 6

 Fyco1

 NM_001106870 Contains a FYVE and spiral coil domain 1

 Fos1

 NM_012953 Analog antigen to fos 1

 Bucs1

 NM 001108502 Butyryl coenzyme A synthetase 1

 Chrnd

 NM 019298 Cholinergic receptor, nicotlnico, delta

 Cacna1c

 ENSRN0T000000093 43 Voltage-dependent calcium channel, type L, subunit 1C

 Symbol

 ID Name

 Slc7a5

 NM 017353 Family 7 solute transporter (Light chain amino acid transporter, system L) member 5

 Myo3b

 NM_001191901 Miosina IIIB

 Myt1

 NM_001108615 Myelin 1 transcription factor

 Aloxe3

 NM 001105793 Araquinodato lipoxygenase 3

 Grm6

 NM_022920 Glutamate receptor, metabotrophic 6

Table 6. Group of 58 genes used to establish the risk of obesity or related alterations. They include: Slbolo, being the official abbreviation of the gene; ID, the identification code of the National Center for 5 Biotechnology Information (NCBI) database; Full official name of the gene in Spanish.

 Slbolo

 ID Name

 Lrp11

 NM_001106217 Protelna related to the low density lipoproteln receptor 11

 Gls

 NM_001109968 Glutaminase

 Ubash3b

 NM_001191792 Contains a domain associated with ubiquitin and SH3, B

 Crmp1

 NM_012932 Protelna mediating the response to collapsin 1

 Gla

 NM_001108820 Galactosidase, alpha

 Paox

 NM 001106311 Polyamine oxidase

 Rnf10

 NM_001011904 RING 10 zinc finger protelna

 Selenbp1

 NM_080892 Protelna of union to selenium 1

 Tmsb4x

 NM_031136 Thymosin beta 4, linked to X

 Smagp

 NM 182817 Small cell adhesion glucoproteln

 Diexf

 NM_001013986 Homologue to the expansion factor of the digestive organ (zebrafish)

 Gabra6

 NM_021841 Receptor A of gamma-aminobutyl acid (GABA), alpha 6

 Fyco1

 NM_001106870 Contains a FYVE and spiral coil domain 1

 Fos1

 NM_012953 Analog antigen to fos 1

 Bucs1

 NM 001108502 Butyryl coenzyme A synthetase 1

 Chrnd

 NM 019298 Cholinergic receptor, nicotlnico, delta

 Cacna1c

 ENSRN0T000000093 43 Voltage-dependent calcium channel, type L, subunit 1C

 Slc7a5

 NM_017353 Family 7 solute transporter (Light chain amino acid transporter, system L) member 5

 Myo3b

 NM_001191901 Miosina IIIB

 Symbol

 ID Name

 Myt1

 NM_001108615 Myelin 1 transcription factor

 Aloxe3

 NM_001105793 Arapoinodate lipoxygenase 3

 Grm6

 NM 022920 Glutamate Receptor, Metabotrophic 6

 Itgal

 NM 001033998 Integrin alfa L

 Prm1

 NM_001002850 Protamine 1

 Pcmtd2

 NM 001107810 Contains a domain of the protein L-isoaspartate (D-aspartate) O-methyltransferase 2

 Crtcl

 NM_001047115 Co-activator 1 of transcription regulated by CREB

 Olr1075

 NM 001000421 Olfactory receiver 1075

 Ctla2a

 NM 001109115 Protelna associated with cytotoxic T 2 lymphocytes

 Olr1500

 NM_001000942 Olfactory Receiver 1500

 Txnip

 NM_001008767 Protelna that interacts with thioredoxin

 Bcap29

 NM 001006980 Protelna associated with the B, 29 cell receptor

 Stk4

 NM 001107800 Serine / threonine kinase 4

 Myc

 NM_012603 Oncogene of myelocytomatosis

 Tsc22d3

 NM 031345 Family of domain TSC22, member 3

 Msh4

 NM 001106477 MutS homologue 4 (from E. coli)

 Zc3h15

 NM_001010963 Contains zinc finger type CCCH 15

 Uri1

 NM_001107507 URI1, chaperone analogous to prefoldin

 Il10

 NM 012854 Interleukin 10

 Zfp503

 NM 001107250 Zinc finger protelna 503

 Ldlrap1

 NM_001109271 Protelna adapter for low density lipoproteln receptor 1

 Cirh1a

 NM 001009640 Cirrhosis, autosomal recessive 1A

 Acp6

 NM 001031645 Phosphatase acid 6, lysophosphatic

 Olr1394

 NM_001001091 Olfactory receiver 1394

 Osbpl1a

 NM 172023 Analog to oxysterol binding protein 1A

 Cd2

 NM 012830 Molecula Cd2

 Bcl2

 NM_016993 Cell B CLL / lymphoma 2

 Meis3

 NM_001108472 Meis homeobox 3

 Serpinf2

 NM_001011892 Serpine peptidase inhibitor, subtype F (alpha-2 antiplasmin, pigment epithelial derived factor), member 2

 Pkia

 FQ211701 Alpha protelna kinase inhibitor (cAMP dependent, catalltica)

 Cd40lg

 NM_053353 Ligand CD40

 Slc9a3r1

 NM 021594 Family 9 solute transporter (sodium / hydrogen exchanger), member 3 regulator 1

 Bcap31

 NM_001004224 Protelna associated with cell receptor B, 31

 Prmt3

 NM_053557 Protelna arginine methyltransferase 3

 Symbol

 ID Name

 Ebpl

 NM_001108381 Analog to the union of the emopamil

 Cd247

 NM_170789 Molecula Cd247

 Wash2

 NM 001127390 Homologue 2 of the WAS family of protelnas

 Tgm1

 NM 031659 Transglutaminase 1, polypeptide K

 Rps19

 NM_001037346 Protelna ribosomal S19

Table 7. Group of the 161 remaining genes used to establish the risk of obesity or related alterations. They include: Slbolo, being the official abbreviation of the gene; ID, the identification code of the 5 National Center for Biotechnology Information (NCBI) database; Full official name of the gene in Spanish.

 Slbolo

 ID Name

 Uba5

 NM_001009669 Activator enzyme of ubiquitin type 5 modifier

 RT1-EC2

 M10094 RT1 lb class, EC2 locus

 RT1-A3

 NM_001008830 RT1 class l, locus A3

 Mpp5

 NM_001108034 Membrane membrane, palmitoylated 5 (member 5 of the MAGUK p55 subfamily)

 Pla2g12a

 NM 001108565 Phospholipase A2, group XIIA

 Glt1d1

 ENSRN0T000000645 26 Contains a glucosyltransferase domain 1

 Stau2

 NM 001007149 Homologue 2 of staufen, RNA binding protein (Drosophila)

 Olr1602

 NM_001000909 Olfactory receiver 1602

 Mtss1

 NM_001130563 Metastatic Suppressor 1

 Vapb

 NM_021847 Protelna B and C associated to VAMP (vesicle associated membrane protelna)

 Ppp1r12c

 NM_001191946 Protelna phosphatase 1, regulatory subunit 12C

 Pacs1

 NM 134406 Protelna 1 involved in the ordering of the acid phosphoforin assembly

 Calr

 NM 022399 Calreticulin

 Txlng

 ENSRN0T000000068 43 Gamma Taxiline

 Satb1

 NM 001012129 SATB homeobox 1

 P4ha2

 NM_001108275 Prolil 4-hydroxylase, alpha II polypeptide

 Olr239

 NM_001000211 Olfactory Receiver 239

 Ifi44l

 XM_227820 Analog to interferon-induced protein 44

 Serpinb6b

 NM_001012214 Serine (or cystel) peptidase inhibitor, subtype B, member 6b

 Dhx32

 NM_001130039 DEAH polypeptide (Asp-Glu-Ala-His) 32

 Symbol

 ID Name

 Ddx50

 NM_001013198 DEAH polypeptide (Asp-Glu-Ala-Asp) 50

 Zpbp2

 NM 001007011 Protelna of union to the zone hunted 2

 Arl5a

 ENSRNOT000000091 81 Analog to ADP 5A ribosylation factor

 Amotl2

 NM_031717 Angiomyotin Analog 2

 Cythl

 NM 053910 Cytohesin 1

 Naplll

 NM_053561 Analog to the nucleosome assembly block 1

 Pfkp

 L25387 Phosphofructokinase, platelet

 The t

 NM 030853 Binder for activation of T cells

 Npr1

 NM_012613 Natriuretic peptide receptor A / guanylate cyclase A (atrionatriuretic peptide receptor A)

 Hpse

 NM_022605 Heparanase

 Slc16a8

 NM 031744 Family 16 solute transporter, member 8 (Carboxylic acid transporter 3)

 Ncor1

 XM_001077495 Nuclear Receiver Corrector 1

 Dmrtc1a

 NM_001025288 C1A family analogous to DMRT

 Avil

 NM 024401 Advilina

 Lcmt1

 NM_199405 Leucine carboxymethyltransferase 1

 Friend1

 BC167749 Adhesion Molecule 1 with Ig type domain

 Cd99l2

 NM 134459 Analog to the CD99 2 molecule

 Fcar

 NM 201992 Fc IgA receptor

 Il15

 NM_013129 Interleukin 15

 Prtn3

 NM_001024264 Proteinase 3

 Olr107

 NM 001000148 Olfactory receiver 107

 Cnga1

 NM 053497 Alpha 1 nucleicide dependent channel

 Eef2

 NM_017245 Elongation factor of eukaryotic translation 2

 Zfp638

 NM_001107868 Zinc Finger Protelna 638

 B3gnt8

 NM_001107492 UDP-GlcNAc: betaGal beta-1,3-N-acetylglucosaminyltransferase 9

 Prpsap1

 NM 022545 Protelna associated with phosphoribosyl pyrophosphate synthetase 1

 Panx1

 NM_199397 Pannexin 1

 Wdr77

 NM_001008771 Repeated domain WD 77

 Gnl1

 NM 212500 Analog to guanine nucleotide binding protein

 Abat

 NM_031003 4-aminobutyrate aminotransferase

 Spo11

 NM_001108964 Homologue of SPO11 meiotic prothena covalently linked to DSB (S. cerevisiae)

 Cd38

 NM 013127 Molecule CD38

 Trmt11

 ENSRNOT000000194 36 Homologue of tRNA methyltransferase 11 (S. cerevisiae)

 Pgrmc1

 NM_021766 Receptor membrane component of

 Symbol

 ID Name

 progesterone 1

 Gar1

 NM 001024306 Homologue of the GAR1 ribonucleoproteln (yeast)

 Nphsl

 NM 022628 Nephrosis 1, congenital, Finnish type

 Olr500

 NM_001000680 500 olfactory receiver

 Rasa4

 XM 002724808 Activator 4 of protelna p21 RAS

 Ets1

 L20681 Homologous 1 of the E26 erytoblastosis v-ets virus oncogene

 Arhgefl

 NM 021694 Rho factor guanine nucleotide exchanger (GEF) 1

 Steap4

 NM 001044265 Member 4 of the STEAP family

 Nt5c3l

 NM_001007723 5'-nucleotidase, cytosolic type-III

 Rps11

 NM_031110 Protelna ribosomal S11

 Ftsjd1

 NM 001106186 Contains the FtsJ domain of methyltransferase 1

 Gstp1

 NM 012577 Glutathione S-transferase pi 2

 Ppp1r9a

 NM_053473 Protelna phosphatase 1, regulatory subunit 9A

 Faah

 NM 024132 Fatty acid amide hydrolase

 Stat4

 NM_001012226 Signal transducer and transcription trigger 4

 Lef1

 NM_130429 Binding factor 1 to lymphoid enhancer

 Rgs1

 NM 019336 Regulator 1 of signaling by protelna G

 Slc34a3

 NM_139338 Family 34 solute transporter (sodium phosphate), member 3

 Pdcd4

 NM 022265 Programmed cell death 4

 Prkcq

 ENSRNOT000000259 01 Protelna quinsa C, tit

 Paqr5

 NM_001014092 Member V of the family of progestin and adiponectin receptors

 Cmtm3

 NM 001106164 Protelna 3 containing a transmembrane domain MARVEL analogous to CKLF

 Chorus 2b

 ENSRNOT000000209 51 Coronina, actin binding protein, 2B

 Icos

 NM_022610 T-cell inducible co-stimulator

 Bmp8a

 NM_001109432 Morphogenetic protein of bone 8a

 Zfp259

 NM_001137646 Zinc Finger Protelna 259

 Kcnmb4

 NM_023960 High-conductance calcium channel activated by calcium, subfamily M, beta member 4

 Nipal1

 NM 001106003 Contains a domain analogous to NIPA 1

 Pigl

 ENSRNOT000000041 13 Phosphatidylinositol glycan anchor biosynthesis, class L

 Zfp709

 NM_153731 Zinc Finger Protelna 709

 Commd7

 NM_001030029 Contains a COMM 7 domain

 Tspan6

 NM 001100672 Tetraspanin 6

 Chpt1

 NM_001007750 Choline phosphotransferase 1

 Symbol

 ID Name

 Ywhaz

 NM 013011 Tyrosine activation protein 3- monooxygenase / tryptophan 5-monooxygenase, zeta polypeptide

 Ret

 NM_001110099 Proto-oncogen ret

 Gipc3

 NM 001109282 Member 3 of the GIPC family that contains the PDZ domain

 Rbm3

 NM_053696 Reason for binding to RNA (RNP1, RRM) protelna 3

 Tcf12

 NM_013176 Transcription factor 12

 St8sia1

 NM 012813 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1

 Nlk

 NM_001191924 Analog kinase to nemo

 Smyd2

 NM_206851 Contains a MYND and SET 2 domain

 Plcg1

 NM_013187 Phospholipase C, gamma 1

 Ctnnal1

 NM_001106649 Catenin (prothine associated with cadherin), analogue alpha 1

 Dnmt3a

 NM 001003958 DNA (cytosine-5 -) - methyltransferase 3 alpha

 Stk33

 ENSRNOT000000195 97 Serine / Threonine Kinase 33

 Mpzl1

 NM_001007728 Analog to the myelin zero protein 1

 Noc2l

 NM 001033897 Homologous associated nucleolar complex 2 (S. Cerevisiae)

 Olr1481

 NM_001000527 Olfactory receiver 1481

 Aph1a

 NM_001014255 Homologue A previous defective farlnge 1 (C. Cerevisiae)

 Dyrk2

 NM_001108100 Phosphorylation-regulated dual specific tyrosine kinase

 Pglyrp4

 NM_001191708 Peptidoglycan recognition protein 4

 Cd2ap

 NM_181475 Protelna associated with CD2

 Il7r

 NM 001106418 Interlequin receiver 7

 Shprh

 NM 001107470 Helicase SNF2 with PHD domain and RING histone linker

 Tgm6

 ENSRNOT000000090 97 Transglutaminase 6

 Hpcal1

 NM_017356 Analog to hypocalcin 1

 Itk

 NM_001108825 IL2 inducible T cell kinase

 Evl

 NM 024147 Analog to Enah / Vasp

 Pafah1b3

 NM_053654 Platelet activating factor acetylhydrolase, isoform 1b, subunit 3

 Cdh19

 NM_001009448 Cadherina 19, type 2

 Plscr2

 NM 001014094 Phospholipid Scramblase 2

 Scnn1b

 NM_012648 Sodium channel, non-voltage dependent, beta

 Unc13d

 NM_138844 Homologue D of UNC-13 (C. elegans)

 Ctsw

 NM 001024242 Cathepsin W

 Nob1

 NM_199086 Homologue 1 of the union to NIN1 / RPN12

 Symbol

 ID Name

 (S. cerevisiae)

 Pstk

 ENSRNOT000000279 67 Similar to phosphoseryl-tRNA kinase

 Upf3b

 NM_001135873 Homologue B of the UPF3 regulator of antisense transcripts (yeast)

 Tsr2

 NM 001115027 TSR2 homologue, of accumulation of rRNA 20S (S. cerevisiae)

 Clgaltl

 NM_022950 Central synthase 1, glycoproteln-N-acetylgalactosamine 3-beta-galactosyltransferase, 1

 Rnf125

 NM 001108424 Zinc finger protelna 125

 Olr439

 NM 001000281 Olfactory receiver 439

 Csnk1g2

 NM_023102 Caselna kinase 1, gamma 2

 Kdm6b

 NM_001108829 Specific lysine demethylase 6B

 Camk4

 NM 012727 Calcium / calmodulin-dependent prothena kinase IV

 Muc5b

 ENSRNOT000000289 67 Mucina 5B oligomerica, gel former in mucus

 Camp

 CB577971 Cathelicidin antimicrobial peptide

 Axin2

 NM_024355 Axina 2

 Churc1

 NM_001106741 Protelna containing the churchill domain

 Ptpn9

 NM 001013040 Protelna tyrosine phosphatase non-receptor type 9

 Zap70

 NM_001012002 Protelna kinase associated with the zeta chain (TCR)

 Slc18a2

 NM_013031 Family 18 solute transporter (vesicular monoamine), member 2

 Kcnq4

 AF249748 Voltage dependent potassium channel, subfamily similar to KQT, member 4

 Tbx3

 NM_181638 Box T 3

 Oxsm

 NM_001100508 3-oxoacil-ACP synthase, mitochondrial

 Phemx

 XM 002725757 Pan-hematopoietic expression

 Mx1

 NM_173096 Resistance to myxovirus (influenza virus) 1

 Znhit6

 NM 001106203 That contains zinc finger type-HIT 6

 RGD15597 24

 ENSRNOT000000478 82 Similar to the ribosomal protein 40S S19

 RGD15643 00

 BC168162 Similar to phosphoseryl-tRNA kinase

 Dgka

 NM 080787 Diacylglycerol kinase, alpha

 Elane

 NM_001106767 Elastase, expressed in neutrophils

 Slc9a9

 XM_001064905 Family 9 solute transporter (sodium / hydrogen exchanger), isoform 9

 Ireb2

 NM 022863 Iron-binding element protelna 2

 Tcrb

 BC091428 T-cell receptor beta chain

 Skap1

 NM_173311 Phosphoprotelnum 1 associated with the src kinase

 I ca

 NM 001107514 Homologue of the headcase (Drosophila)

 Adsl

 NM_001130503 Adenilosuccinate liasa

 Symbol

 ID Name

 Slc12a7

 NM_001013144 Family 12 solute transporter (Potassium / chloride transporters), member 7

 Gnpnatl

 NM 001134757 Glucosamine phosphate N-acetyltransferase 1

 Sirt5

 NM 001004256 Sirtuin 5

 Il21r

 NM_001012469 Interlequin Receiver 21

 Gdi1

 NM 017088 GDP 1 dissociation inhibitor

 Eif3e

 NM 001011990 Initiation factor 3 of eukaryotic translation, subunit E

 Nol9

 ENSRNOT000000135 35 Nucleolar Protelna 9

 Gart

 BC087644 Phosphoribosylglycinamide formyltransferase

 Mthfr

 ENSRNOT000000113 84 Methylenetetrahydrofolate reductase (NAD (P) H)

 Isca1

 NM 181626 Homologue to the iron-sulfur center scaffolding project 1 (S. cerevisiae)

 Irx3

 NM_001107413 Iroquois homeobox 3

Claims (79)

5 10 fifteen twenty 25 30 1. Method of obtaining useful data for the prediction and / or prevention of overweight, obesity and / or its complications, which includes the detection and / or quantification of an expression product of the Lrp11 gene in an isolated biological sample of a subject. 2. Method according to claim 1 wherein also an expression product of the Gls and / or Ubash3b gene is detected and / or quantified. 3. Method according to claim 2 where the Lrp11, Gls and Ubash3b genes are detected and / or quantified. 4. Method according to any one of claims 1 to 3, in which an expression product of at least one of the genes selected from the list comprising Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x is also detected and / or quantified. , or any of its combinations. 5. Method according to claim 4 wherein an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x genes is detected and / or quantified. 6. Method according to any of claims 4 or 5 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1 , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any combination thereof. 7. Method according to claim 6 where an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1 genes is detected and quantified , Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6. 8. Method according to any of claims 5 or 6 which further comprises the detection and / or quantification of an expression product of at least one of the 5 10 fifteen twenty 25 30 35 genes that are selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtcl, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfp503, Ldlrap1, Cirh, Ach1, Cirh, Ach1, Cirh, Ach1, Cirh Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof. 9. Method according to claim 8 wherein an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1 genes is detected and quantified Chrnd Cacna1c Slc7a5 Myo3b Myt1 Aloxe3 Grm6 Itgal Prm1 Pcmtd2 Crtc1 Olr1075 Ctla2a Olr1500 Txnip Bcap29 Stk4 Myc Tsc22d3 , Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19. 10. Method according to any of claims 8 or 9 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising the genes described in Table 7. 11. Method according to claim 10 wherein a product of expression of the genes described in Table 1 is detected and / or quantified. 12. Method according to any one of claims 1 to 11 wherein the complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications. 13. Method according to any one of claims 1 to 12 wherein the expression product is mRNA. 14. Method according to any one of claims 1 to 13 wherein the biological sample is selected from the list comprising blood, peripheral blood, cardiac blood, serum umbilical cord blood, saliva, urine and lymph. 5 10 fifteen twenty 25 30 35 15. Method according to any of claims 1 to 14 wherein the subject is a neonate. 16. Method according to any one of claims 1 to 15 wherein the subject is a human. 17. In vitro method for prediction and / or prevention of overweight, obesity and / or its complications in a subject comprising: to. the detection and / or quantification of an expression product of the Lrp11 gene in a biological sample isolated from a subject; b. the association of the detection of a significant alteration of the expression to a bad prognosis. 18. In vitro method according to claim 17 wherein also in step a) a Gls and / or Ubash3b expression product is detected and / or quantified; and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. 19. In vitro method according to claim 18 wherein in step a) an expression product of Lrp11, Gls and Ubash3b is detected and / or quantified; and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. 20. In vitro method according to any one of claims 17 to 19, wherein also in step a) an expression product of at least one of the genes selected from the list comprising: Crmp1, Gla, is detected and / or quantified. Paox, Rnf10, Selenbp1 and Tmsb4x, or any of their combinations and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. 21. In vitro method according to claim 20 wherein the genes detected and / or quantified and whose alteration of the expression is associated with a poor prognosis are Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x. 22. In vitro method according to any of claims 20 or 21 wherein also in step a) an expression product of at least one of the genes selected from the list comprising: Smagp, Diexf, is detected and / or quantified. Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or 5 10 fifteen twenty 25 30 35 any of its combinations and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. 23. In vitro method according to revindication 22 where the genes detected and / or quantified and whose alteration of expression is associated with a poor prognosis are Lrp11, Gls, Ubash3b, Crmpl, Gla, Paox, Rnf10, Selenbpl, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6. 24. In vitro method according to any of claims 22 or 23 wherein also in step a) an expression product of at least one of the genes selected from the list comprising: Itgal, Prm1, is detected and / or quantified. Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Mepis1, P22, P2p1a, B2p1a, Mebis1 Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any of their combinations and in stage b) the alteration of the expression of said genes is associated with a poor prognosis. 25. In vitro method according to revindication 24 where the genes detected and / or quantified and whose alteration of expression is associated with a poor prognosis are: Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp , Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap3, Tscad M4 , Zc3h15, Uri1, Il10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd1, Rb2 26. In vitro method according to any one of claims 24 or 25 wherein also in step a) an expression product of at least one of the genes selected from the list comprising the genes described in the method is detected and quantified. Table 7 and in stage b) the alteration in the expression of said genes is associated with a poor prognosis. 27. In vitro method according to revindication 26 where in step a) an expression product of the genes described in Table 1 and in the sample is detected and / or quantified 5 10 fifteen twenty 25 30 35 stage b) an alteration in the expression of said genes is associated with a poor prognosis. 28. In vitro method according to any one of claims 17 to 27, wherein the complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome, liver Fatty, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis, and psychiatric complications. 29. In vitro method according to any of claims 17 to 28 wherein the expression product is mRNA. 30. In vitro method according to any of claims 17 to 29 wherein the biological sample is selected from the list comprising blood, peripheral blood, cardiac blood, umbilical cord blood, saliva, urine and lymph. 31. In vitro method according to any one of claims 17 to 30 wherein the subject is a newborn. 32. In vitro method according to any of claims 17 to 31 wherein the subject is a human. 33. In vitro method for designing an individualized treatment for a subject comprising detecting and / or quantifying the expression product of the Lrp11 gene in a biological sample; in which the alteration of the expression is indicative that the treatment to be administered is leptin or a composition comprising leptin. 34. In vitro method according to revindication 33 where also an expression product of the Gls and / or Ubash3b genes is detected and quantified and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. 35. In vitro method according to revindication 34 where an expression product of the Lrp11, Gls and Ubash3b genes is detected and quantified and where the alteration of 5 10 fifteen twenty 25 30 35 the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. 36. In vitro method according to any one of claims 33 to 35, in which an expression product of at least one of the genes selected from the list comprising Crmpl, Gla, Paox, Rnf10, Selenbpl is also detected and / or quantified. and Tmsb4x, or any combination thereof and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. 37. In vitro method according to claim 36 where an expression product of the Lrp11, Gls, Ubash3b, Crmpl, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x genes is detected and quantified and wherein the alteration of the expression of said genes It is indicative that the treatment to be administered is leptin or a composition comprising leptin. 38. In vitro method according to any of claims 36 or 37 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1 , Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any combination thereof and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin . 39. In vitro method according to claim 38 where an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1 genes is detected and / or quantified. , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6 and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. 40. In vitro method according to any of claims 38 or 39 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtc1 , Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, 5 10 fifteen twenty 25 30 35 Osbplla, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof and where the alteration of the expression of these genes is indicative that the Treatment to be administered is leptin or a composition comprising leptin. 41. In vitro method according to claim 40 wherein an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1 genes is detected and / or quantified. , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Z3103, Mh4, Z3p3, Mh4, Z3p3, Mh4, Z3p3, Md4, 3, M3 , Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19 and where the expression of the alteration is indicated that the treatment to be administered is leptin or a composition comprising leptin. 42. In vitro method according to any of claims 40 or 41 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising the genes described in Table 7 and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. 43. In vitro method according to claim 39 where a gene expression product described in Table 1 is detected and / or quantified and where the alteration of the expression of said genes is indicative that the treatment to be administered is leptin or a composition comprising leptin. 44. In vitro method according to any one of claims 33 to 43 wherein the composition comprising leptin is breast milk. 45. In vitro method according to any of claims 33 to 44 wherein the complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, hypertriglyceridemia dyslipidemia, hypercholesterolemia, metabolic syndrome, fatty liver , hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis and psychiatric complications. 5 10 fifteen twenty 25 30 35 46. In vitro method according to any of claims 33 to 45 wherein the expression product is mRNA. 47. In vitro method according to any of claims 33 to 46 wherein the biological sample is selected from the list comprising blood, peripheral blood, cardiac blood, umbilical cord blood, saliva, urine and lymph. 48. In vitro method according to any one of claims 33 to 47 wherein the subject is a neonate. 49. In vitro method according to any one of claims 33 to 48 wherein the subject is a human. 50. In vitro method of evaluating the effectiveness of a treatment with leptin or a composition comprising leptin comprising the detection and / or quantification of an expression product of the Lrp11 gene in a biological sample isolated from a subject that has received said treatment. 51. In vitro method according to claim 50 where the expression product of the Gls and / or Ubash3b genes is also detected and / or quantified. 52. In vitro method according to claim 51 where the expression product of the Lrp11, Gls and Ubash3b genes is detected and / or quantified. 53. In vitro method according to any one of claims 50 to 52, in which an expression product of at least one of the genes selected from the list comprising: Crmp1, Gla, Paox, Rnf10, Selenbp1 is also detected and / or quantified. and Tmsb4x, or any of its combinations. 54. In vitro method according to claim 53 wherein an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x genes is detected and / or quantified. 55. In vitro method according to any of claims 50 to 54 which further comprises the detection and / or quantification of an expression product of at 5 10 fifteen twenty 25 30 35 minus one of the genes that are selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or any combination thereof. 56. In vitro method according to claim 55 wherein an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1 genes is detected and / or quantified. , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6. 57. In vitro method according to any one of claims 55 or 56 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtc1 Olr1075 Ctla2a Olr1500 Txnip Bcap29 Stk4 Myc Tsc22d3 Msh4 Zc3h15 Uri1 Il10 Zfp503 Ldlrap1 Cirh1a Acp6 Olr1394 Osbpl1a Cd2 Cd2 , Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19, or any combination thereof. 58. In vitro method according to claim 57 where an expression product of the Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1 genes is detected and / or quantified. , Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Z3103, Mh4, Z3p3, Mh4, Z3p3, Mh4, Z3p3, Md4, 3, M3 , Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19. 59. In vitro method according to any of claims 57 or 58 which further comprises the detection and / or quantification of an expression product of at least one of the genes that are selected from the list comprising the genes described in Table 7. 60. In vitro method according to claim 59 where a gene expression product described in Table 1 is detected and / or quantified. 61. In vitro method according to any of claims 50 to 60 wherein the expression product is mRNA. 5 10 fifteen twenty 25 30 35 62. In vitro method according to any one of claims 50 to 61 wherein the biological sample is selected from the list comprising blood, peripheral blood, cardiac blood, umbilical cord blood, saliva, urine and lymph. 63. In vitro method according to any of claims 50 to 62 wherein the subject is a neonate. 64. In vitro method according to any one of claims 50 to 63 wherein the subject is a human. 65. Use of the Lrp11 gene expression product as a biomarker for the prediction and / or prevention of overweight, obesity and / or its complications in a subject. 66. Use according to claim 65 which further includes the use of the product of expression of the Gls and / or Ubash3b genes. 67. Use according to claim 66 wherein the genes are Lrp11, Gls and Ubash3b 68. Use according to any of claims 65 to 67 wherein the genes are also selected from the Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x list, or any combination thereof. 69. Use according to claim 68 where the genes are: Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1 and Tmsb4x. 70. Use according to any of claims 68 or 69 wherein the genes are also selected from the list comprising: Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7a5, Myo3b, Myt1, Aloxe3 and Grm6, or Any of your combinations. 71. Use according to claim 70 wherein the genes are Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7b5, Myo3t, Myyo3 , Aloxe3 and Grm6. 5 10 fifteen twenty 25 30 35 72. Use according to any of claims 70 or 71 wherein the genes are also selected from the list comprising: Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15 , Uri1, Il10, Zfp503, Ldlrap1, Cirh1a, Acp6, Olr1394, Osbpl1a, Cd2, Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd24m or combinations of R219, combinations . 73. Use according to claim 72 where the genes are Lrp11, Gls, Ubash3b, Crmp1, Gla, Paox, Rnf10, Selenbp1, Tmsb4x, Smagp, Diexf, Gabra6, Fyco1, Fosl1, Bucs1, Chrnd, Cacna1c, Slc7b5, Myo3t, Myyo3, Myo3 , Aloxe3, Grm6, Itgal, Prm1, Pcmtd2, Crtc1, Olr1075, Ctla2a, Olr1500, Txnip, Bcap29, Stk4, Myc, Tsc22d3, Msh4, Zc3h15, Uri1, Il10, Zfp503, Ldlrap1, Cirh1pd, Cd1pd1, Cirh1pd, Cd1pd1, Cirh1pd, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1, Cd1p1 , Bcl2, Meis3, Serpinf2, Pkia, Cd40lg, Slc9a3r1, Bcap31, Prmt3, Ebpl, Cd247, Wash2, Tgm1 and Rps19. 74. Use according to any of claims 72 or 73 which further comprises the genes described in Table 7. 75. Use according to claim 74 where it also comprises the genes described in Table 1. 76. Use according to any of claims 65 to 75 wherein the expression product is mRNA. 77. Use according to any of claims 65 to 76 wherein the complications are selected from the list comprising: type 2 diabetes, insulin resistance, leptin resistance, hyperphagia, dyslipidemia, hypertriglyceridemia, hypercholesterolemia, metabolic syndrome, fatty liver, hypertension, cardiovascular disease, obstructive sleep apnea, cancer, arthritis, osteoarthritis, and psychiatric complications. 78. Use according to any of claims 65 to 77 wherein the subject is a newborn. 79. Use according to any one of claims 65 to 78 wherein the subject is a human.