WO2007079386A2

WO2007079386A2 - Method of diagnosing a body weight condition or predisposition in an animal

Info

Publication number: WO2007079386A2
Application number: PCT/US2006/062640
Authority: WO
Inventors: William D. Schoenherr; Cheryl C. Miller; Kim G. Friesen; Philip W. Toll
Original assignee: Hill's Pet Nutrition, Inc.
Priority date: 2005-12-28
Filing date: 2006-12-28
Publication date: 2007-07-12
Also published as: WO2007079386A3; CN101427134A

Abstract

A method for diagnosing a body weight condition or predisposition to a body weight condition in an animal by determining observed level(s) of at least one biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker: wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition.

Description

METHOD OF DIAGNOSING A BODY WEIGHT CONDITION OR PREDISPOSITION

BACKGROUND OF THE INVENTION

Field of the Invention

[0001] The present invention relates to methods of diagnosing a body weight condition or predisposition in an animal.

Description of the Prior Art

[0002] The prevalence of obesity has increased in both human and non-human populations. Obesity rates in humans are of epidemic proportions. Furthermore, studies show that 25% to 40% of all American household pets are overweight or obese, a trend that is leading to a steady rise in overweight-related pet illnesses and increased veterinary costs. [0003] Being overweight can be a risk factor for development of a variety of disorders or diseases. Obesity, for example, has been linked to heart disease, degenerative joint disease, diabetes and cancer, among other conditions. Further, an overweight animal may experience considerable problems through reduced mobility and decreased overall quality of life. Prevention of an overweight condition can have a lifelong impact and knowledge of the risk factors for development of such a condition can lead to improved prevention and treatment programs that optimize overall health.

[0004] Various biomarkers, including for example plasma leptin. have been associated with food intake and body fat. Shiiya et al. (2002) J. Clin. Endocrinol. Mctab. 87(l):240- 244 reported that plasma ghrelin concentrations were lower in obese than in lean humans. [0005] Despite awareness of the health implications of an overweight condition, treating such a condition remains a challenge due to. among other things, little understanding of the underlying physiological mechanisms or changes that occur in physiological systems that maintain such a condition. Measurement of body weight by traditional techniques is helpful, but the information thus gained is crude and may provide little insight into underlying physiological or biochemical processes associated with a body weight condition such as obesity. Furthermore, such traditional techniques have limited value in detecting or diagnosing a predisposition to obesity or other body weight condition in an animal having norma! body weight. There remains a need for effective methods of diagnosing a body weight condition or predisposition in an animal. SUMMARY OF THE INVENTION

[0006] The invention provides a method for diagnosing a body weight condition or predisposition thereto in an animal. The method comprises determining observed level(s) of at least one biomarker in a tissue or biofluid sample from the animal and comparing the observed level(s) to reference level(s) for the biomarker, wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition.

[0007] There is further provided a method for selecting a regimen for an animal. The method comprises (a) diagnosing a body weight condition or predisposition thereto by determining observed level(s) of at least one biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker: wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition; and (b) identifying a regimen appropriate to the body weight condition or predisposition diagnosed. [0008] There is still further provided a method for detecting onset of a body weight condition or predisposition in an animal. The method comprises monitoring at least one biomarker in the animal over a period by determining, at each of a plurality of time points during the period, observed level(s) of the biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker; wherein onset is detected if, at any time point, the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition. [0009] There is still further provided a method for assessing the efficacy of a regimen for managing a body weight condition or predisposition in an animal. The method comprises monitoring at least one biomarker in the animal over a period during which the regimen is administered, by determining, at each of a plurality of time points during the period, observed level(s) of the biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker; wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the efficacy of the regimen in managing the body weight condition or predisposition. (0010] There is still further provided a kit comprising:

(a) one or more reagents for detecting observed level(s) of at least one biomarker in a tissue or biofluid sample from an animal; and (b) one or more user-accessible media carrying information that comprises (i) reference level(s) of the biomarker; and (ii) an algorithm that compares the observed level(s) to the reference level(s); wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of a body weight condition or predisposition in the animal. [0011] Additional objects, features, and advantages of the invention will be apparent to those skilled in the art.

DETAILED DESCRIPTION OF THE FNVENTlON

[0012] It has been found in accordance with the invention that levels of certain biomarkers in a tissue or biofluid sample from an animal can be surprisingly effective in diagnosis of a body weight condition in the animal. Levels of such biomarkers can fluctuate from a preprandial to a postprandial state. However, individual animals with different body weight conditions, e.g., lean and obese animals, show differences in the form and/or degree of such fluctuation, as well as in absolute levels of the biomarkers when in a fasted state. Profiles of one or more biomarkers. therefore, can be indicative of a body weight condition. Further, such profiles are indicative of a predisposition to a body weight condition, even where that condition is not yet expressed. Such profiles are useful in managing an animal's body weight and health consequences that may be associated with a body weight condition existing in the animal or to which the animal is predisposed.

[0013] Biomarkers of interest herein are those for which an observed level relative to a reference level is indicative of a body weight condition or predisposition. According to some embodiments, a reference level can be established from samples obtained from healthy animals of normal body weight, or can be a published value. Typically, reference levels are established for animals of the same species and. if possible, breed or breed type. Further, it is generally preferable that reference levels are established for animals of similar age group to the animal. In this case, an observed level substantially different from (e.g.. higher or lower than) the reference level can be indicative of a body weight condition or predisposition. Such a difference can be. but is not necessarily, statistically significant. [0014] Alternatively, a reference level can be established for animals known to have a particular body weight condition or predisposition; an observed level similar to the reference level can in this case be indicative of the condition or predisposition. [0015] The level of a biomarker can provide information about underlying genetic, biochemical or physiological factors, mechanisms or pathways associated with a particular existing body weight condition (e.g., normal weight, overweight, obese), but is not necessarily informative in this way. In some cases, a statistical correlation between a level of a biomarkcr and an observed body weight condition or predisposition can suffice for practice of the invention. However, where the biomarker provides information of genetic, biochemical or physiological relevance, advantages over traditional methods relying solely on physical measurements related to body weight can be especially great. [0016] The animal can be human or non-human. In various embodiments, the animal is a vertebrate, for example a fish, a bird, a reptile or a mammal. Illustratively among mammals, the animal can be a member of the order Carnivora. including without limitation canine and feline species.

[0017] In an embodiment, the animal is a companion animal. A "companion animal'^" herein is an individual animal of any species kept by a human caregiver as a pet. or any individual animal of a variety of species that have been widely domesticated as pets, including dogs (Canis familiaris) and cats (Felis domesticus), whether or not the individual animal is kept solely or partly for companionship. Thus "companion animals" herein include working dogs, farm cats kept for rodent control, etc., as well as pet dogs and cats. In some embodiments, the animal is a canine. In other embodiments, the animal is a feline. [0018] A body weight condition diagnosed according to the invention can be an underweight, normal weight or overweight, including obese, condition. Body weight is generally not simply a matter of weight alone, but is usually associated with quantity or percentage of body fat. See for example Burkholder & Toll (2000) in Hand et al. (eds.). Small Animal Clinical Nutrition. 4th Edition. Chapter 13. pp 402-430. [0019] A '"body weight predisposition" herein refers to an animal's proneness (i.e.. propensity) for gaining, losing, or maintaining body weight and/or undergoing concomitant changes in health or other physiological conditions. Thus examples of body weight predispositions include a propensity, or lack thereof, to gain weight and a predisposition to obesity.

[0020] According to one embodiment, a body weight predisposition is diagnosed by a method of the invention while the animal is young, for example, in the case of a canine or feline, up to about one year of age.

[0021 ] An overweight or obese condition can be an associative cause or exacerbating factor for a number of diseases and disorders including, for example, metabolic alterations, endocrinopathies, functional alterations, degenerative joint and orthopedic diseases. cardiovascular diseases, cancers, sleep disorders, reproductive disorders, and combinations thereof. An overweight condition also can cause considerable problems through reduced mobility or decreased quality of life. In one embodiment, therefore, a body weight condition or predisposition diagnosed by practice of the invention is one that increases the animal's risk for an overweight-related health disorder.

[0022] Such overweight-related heath disorders illustratively include hyperlipidemia, dyslipidemia. insulin resistance, glucose intolerance, hepatic lipidosis, anesthetic complications, hyperadrenocorticism. hypothyroidism, diabetes mellitus. insulinoma, pituitary chromophobe adenoma, hypopituitarism, hypothalamic lesions, joint stress, musculoskeletal pain, dyspnea, hypertension, dystocia, exercise intolerance, heat intolerance, decreased immune function, degenerative joint and orthopedic diseases, cardiovascular diseases, transitional cell carcinomas, fatigue, sleep disorders, reproductive disorders, and combinations thereof.

[0023| The term "biomarker" means a substance that can be quantitatively identified in a tissue or biofluid sample and that provides a correlation to a particular phenotype or physiological condition. Illustratively, a biomarker can be a cytokine, e.g., an inflammatory cytokine; a peptide or protein, e.g.. peptide YY, neuropeptide Y. glucagon-like peptide 1 (GLP-I), ghrelin; a nucleic acid, e.g.. an mRNA transcript corresponding to a peptide or protein biomarker. a biochemical metabolite, e.g., glucose: a neurotransmitter; an agonist: or an antagonist. In various embodiments, level(s) of at least one of the following biomarkers are determined: glucose. GLP-I, ghrelin. leptin, adiponectin, resistin, resistin- like molecules, and insulin. Particularly useful biomarkers include glucose, GLP- I and ghrelin.

[0024| Diagnosis of a body weight condition or predisposition by the method of the invention can involve determination of more than one biomarker. In some cases, a single biomarker can be indicative of the body weight condition or predisposition: in other cases, a biomarker profile, comprising levels of two or more biomarkers, is collectively indicative of the condition or predisposition.

[0025] Any tissue or biofluid sample can be a source of biomarkers of interest. However, in most cases biofluid samples that can be obtained with minimal invasion are preferred. Biofluids illustratively include whole blood, blood serum, blood plasma, cerebrospinal fluid, crevicular fluid, urine, lymph fluid, intramuscular fluid, nasal secretion and saliva. [0026] A level of a biomarker can be determined using assays known in the art. An assay can. but need not. be a commercially available assay. Typically, an assay is chosen based on the type of biomarker and the type of sample. For example, a commercially available monoclonal-based immunoassay utilizing monoclonal antibodies reactive to one or more epitopes on polypeptides or a competitive binding assay can be used for determining a blood serum level of a protein biomarker such as. for example, GLP-I or ghrelin; and an assay based on a ferrϊcyanide. hexokinase, or glucose oxidase procedure can be used for determining a blood serum level of glucose.

[0027] In some embodiments, observed and/or reference levels are determined using one or more assays independently selected from the group consisting of enzyme immunoassays (ElA), enzyme-linked immunosorbent assays (ELISA). immunofluorescent assays (IFA), radioimmunoassays (RIA), western blot assays, biochemical assays, enzymatic assays, and colorimetric assays. A variety of labels and conjugation techniques are known by those skilled in the art and can be used in the various biochemical, nucleic acid and amino acid assays.

[0028] A tissue or biofluid sample can be collected, for example, at a point of care facility, i.e., a place where an animal can be seen by a health care practitioner (e.g., medical doctor, veterinarian, medical assistant, physician's assistant, nurse, etc.) for evaluation and diagnosis. Non-limiting examples of a point of care facility include a hospital, office of a physician or veterinarian, and veterinary clinic. Alternatively, a sample can be collected at the animal^'s home, farm, stable or barracks where the animal is kept. [0029J Analysis of the sample for the one or more biomarkers of interest can be done at the place, e.g., point of care facility, where the sample is taken. A kit as described herein can be used in such analysis. Alternatively, the sample can be sent to a secondary facility. The term "secondary facility" means a laboratory such as a commercial testing laboratory where clinical samples are evaluated, and can be off-site (i.e.. at a different location) from a point of care facility.

[0030] In some embodiments, comparing the observed level(s) to reference level(s) of the one or more biomarkers is performed at a point of care facility or a secondary facility. [0031] Where a sample is taken at a single time point, this can be at any stage of the animal's feeding cycle, for example immediately before a meal (preprandial) or at a suitable interval after a meal (postprandial). However, it is generally preferred that when diagnosis is to be based on a single sample, that such sample be taken when the animal is in a fasting state, for example at a preprandial time point.

[0032] Optionally, samples arc taken at a plurality of time points during the feeding cycle.

In this case, at least one (typically just one) preprandial sample and at least one (typically more than one) postprandial sample can be taken. Suitable time points arc illustratively 0

(preprandial). 10. 30, 60. 120 and 360 minutes postprandial.

[0033] Biomarker levels in a sample, for example a serum sample, can be unadjusted, or adjusted for body weight of the animal. Unadjusted levels can be expressed in weight/volume concentration units such as mg/1, μg/l or ng/1, or molar concentration units such as μmol/1. nmol/1 or pmol/l. Adjusted levels can be expressed in similar units, but with body weight (BW) as a divisor, e.g., mg/I/kg BW. pmol/1/kg BW, etc.

]0034] In one embodiment, the animal is canine and the biomarker comprises glucose in serum. According to this embodiment, an observed body weight-adjusted serum glucose level in a fasted animal at least about 10% lower than the body weight-adjusted reference level for a canine of normal weight is indicative of a predisposition of the animal to gain weight.

|0035] In another embodiment, the animal is canine and the biomarker comprises GLP-I in serum. According to this embodiment, an observed body weight-adjusted serum GLP-I level in a fasted animal at least about 20% lower than the body weight-adjusted reference level for a canine of normal weight is indicative of a predisposition of the animal to gain weight.

[0036] In yet another embodiment, the animal is canine and the biomarker comprises ghrelin in serum. According to this embodiment, an observed body weight-adjusted serum ghrelin level in a fasted animal at least about 20% lower than the body weight-adjusted reference level for a canine of normal weight is indicative of a predisposition of the animal to gain weight.

[0037] Upon diagnosis of a body weight condition or predisposition as described above, a regimen appropriate to the condition or predisposition can be selected. The regimen can be selected by the animal or the animal's caregiver based on information communicated by any suitable communication means, or can be prescribed by a health care professional. The regimen can comprise one or more of diet, exercise, and medication.

[0038] In some embodiments, a regimen comprises a composition for consumption by the animal. Illustratively, such a composition can be a nutritional composition, such as a food composition, a supplement, a treat or a toy. it being noted that some, but not all. supplements, treats and toys are themselves food compositions. Food compositions can be. for example, ingested by an animal or administered to an animal by feeding. Where the animal is a companion animal, a food composition useful in the method of the invention is typically one that is nutritionally adapted for feeding to such an animal (referred to herein as a ''pet food^") and is appropriate for the body weight condition or predisposition diagnosed. Pet foods can be more particularly adapted to the special nutritional needs of canines or felines, or to certain subpopulations thereof such as large-breed dogs, puppies or kittens, young dogs or cats, adult dogs or cats, senior dogs or cats, and geriatric dogs or cats. [0039] A food composition forming part of a regimen can be one providing a substantially nutritionally complete diet for the animal. A "nutritionally complete diet" is a diet that includes sufficient nutrients for maintenance of normal health of a healthy animal on the diet.

[0040] Alternatively, the composition can be a supplement, i.e.. a composition used with another food composition to improve the nutritive balance or performance of the diet as a whole. Such supplements include food compositions that are fed undiluted as a supplement to other foods, offered free choice with other parts of an animal's ration that are separately available to the animal, or diluted and mixed with an animal's regular food to produce a substantially nutritionally complete diet. Supplements can alternatively be in a form other than a food composition, for example in a pharmaceutical-like dosage form including, for example, powders, liquids, syrups, pills, etc.

[0041 ] The composition can be a treat. Treats include, for example, compositions given to an animal as a reward or to entice the animal to eat during a non meal time. Treats for dogs that are food compositions having at least some nutritional value include, for example, dog biscuits. Treats can alternatively be substantially non-nutritional. A composition forming part of a regimen can itself form a treat, be coated onto an existing treat, or both. [0042] The composition can be a toy adapted for oral use by an animal. To>s include, for example, chewable toys, such as artificial bones for dogs. A composition useful herein can form a coating on the surface of a toy or on the surface of a component of a toy. be incorporated partially or fully throughout the toy, or both. A wide range of suitable toys are currently marketed, including partially consumable toys (e.g., toys comprising plastic components) and fully consumable toys (e.g.. rawhides and various artificial bones). Toys are available for human and non-human use. particularly for companion, farm, and zoo animal use. and more particularly for dog. cat. or bird use.

[0043] In other embodiments, a regimen comprises a form of exercise. Exercise can take any form suitable for the animal and appropriate for the body weight condition or predisposition diagnosed. Illustratively, exercise can include without limitation walking, jogging or running.

[0044] The regimen can be continued at a frequency or for a period of time as is necessary or appropriate for the body weight condition or predisposition. Illustratively, a regimen can continue for at least about 1 month, at least about 2 months, at least about 6 months, at least about 1 year, or for some other period of time as may be determined necessary or appropriate, for example by a veterinarian or other health care professional. [0045] The invention also provides a method for detecting onset of a body weight condition or predisposition in an animal. According to this method, at least one biomarker in the animal is monitored over a period, and onset is detected if, at any time point during that period, the observed level(s) relative to the reference level(s) of the biomarker are individually or collectively indicative of the body weight condition or predisposition. [0046] Such a method optionally further comprises monitoring the animal's body weight during at least part of the period. Any appropriate technique for determining body weight can be used, including without limitation weighing, assessment of relative body weight (RBW). assessment of body condition score (BCS). morphometry, and combinations thereof. Additional useful information relating to body weight can optionally be obtained by techniques such as magnetic resonance imaging (MRI). computerized tomography (CT), neutron activation, hydrodensitometry, total body water by isotope dilution, total body potassium, ultrasound, bioelectrical impedance, radiograph, sonograph, dual energy x-ray absorptiometry (DEXA). or combinations thereof.

[0047] Monitoring of the biomarker, and optionally of body weight and/or other related parameters, can be performed at any convenient interval, for example at about hourly, twice daily, daily, twice weekly, weekly, monthly, bimonthly, twice yearly or yearly intervals. [0048] Monitoring of the biomarker can also provide a useful method for assessing the efficacy of a regimen for managing a body weight condition or predisposition in an animal. According to this method, the biomarker, and optionally body weight and/or other related parameters, are monitored over a period during which the regimen is administered. The observed level(s) relative to the reference level(s) of the biomarker can be individually or collectively indicative of the efficacy of the regimen in managing the body weight condition or predisposition.

[0049J In another embodiment of the invention, a kit is provided, suitable for use according to any of the methods described herein. Such a kit comprises one or more reagents for detecting observed level(s) of at least one biomarker in a tissue or biofluid sample from an animal; and one or more user-accessible media carrying information that comprises (i) reference level(s) of the biomarker: and (ii) an algorithm that compares the observed level(s) to the reference level(s). As in previous embodiments, the observed level(s) relative to the reference levei(s) are individually or collectively indicative of a body weight condition or predisposition in the animal.

|0050| "User-accessible" media herein include all media, such as paper, disk, memory chip, card, computer or network, on which instructions, information, an algorithm and/or data can be retrievably contained or stored. The algorithm is typically a software algorithm. [00511 The kit is optionally self-contained so as not to require laboratory equipment. Optionally, the kit further comprises a tissue or biofluid sample collection device. The kit can employ one or more of a variety of assays for determining a level of a biomarker, including the assays listed above. Standards and standard additions can be included and used for calibration in quantifying the level of a biomarker in a sample, using well known techniques.

[0052] In some embodiments, the one or more reagents of the kit comprise a reporter moiety or label. The reporter moiety or label can illustratively comprise biotin. a chromogenic agent, a luminescent or chemiluminescent, a cofactor, an enzyme, a fluorescent agent, an inhibitor, a metal or magnetic particle, a radionuclide, a substrate or a combination thereof, and can be detected using methods known in the art. Illustratively, such methods include without limitation spectroscopic methods used to detect dyes (including, for example, colorimetric detection of products of enzyme reactions), luminescent groups and fluorescent groups: detection of enzyme reporter groups by addition of a substrate, followed by spectroscopic, spectrophotometry or other analysis of reaction products: scintillation counting or autoradiographic methods for radioactive groups; and Raman scattering techniques for metal nanoparticles (e.g.. gold nanoparticles). [0053] The one or more reagents of a kit can comprise at least one antibody, for example a polyclonal or monoclonal antibody. The antibody can be immobilized on a solid support. For example, an ELISA can be utilized to determine a level of a biomarker in a sample. The ELISA can involve coupling an antibody onto a solid support such as a polymer. A sample comprising a biomarker can be introduced and the biomarker alloλved to interact with the antibody, whereupon a signal (e.g., chroniogenic signal) generating process can be performed to create an optically detectable signal.

[0054] In one embodiment, the kit comprises a first antibody that specifically binds to the biomarker in the sample, and a second antibody that specifically binds to the resulting complex of the first antibody and the biomarker. The second antibody can be immobilized to a solid support. For example, upon binding of the second antibody to the first antibody/biomarker complex, the second antibody can trigger a reaction and. for example, result in a detectable color change.

[0055] A variety of labels and conjugation techniques are known by those skilled in the arts. Techniques for producing labeled hybridization or PCR probes for detection and quantification of nucleic acid sequences include oligo-labeling, nick translation, end- labeling and PCR amplification using a labeled nucleotide. Alternatively, the coding sequence of a biomarker. or any portion thereof, may be cloned into a vector for production of an mRNA probe. Such vectors are known in the art. are commercially available, and can be used to synthesize RNA probes in vitro by addition of an appropriate RNA polymerase such as T7. T3 or SP6, and labeled nucleotides.

[0056] The kit optionally further comprises means for communicating information comprising one or more of (a) a diagnosis of a body weight condition or predisposition as indicated by the observed level(s) relative to the reference level(s) of the biomarker: and (b) a suggested or prescribed regimen appropriate to the diagnosis.

[0057] The communicating means can be attached to or enclosed in a package containing other elements of the kit. Any suitable form of communicating means can be employed, for example a document such as a label, brochure, advertisement or package insert, a computer- readable digital or optical medium such as a diskette or CD, an audio presentation, for example on an audiotape or CD, or a visual presentation, for example on a videotape or DVD. The communicating means can refer to further information located elsewhere, such as on a website.

[0058] Such a communicating means, comprising for example a document such as a label, brochure, advertisement or package insert, a computer-readable digital or optical medium such as a diskette or CD. an audio presentation, for example on an audiotape or CD, a visual presentation, for example on a videotape or DVD. and/or one or more pages on a website, is itself a stil! further embodiment of the invention.

[0059] The invention is not limited to the particular methodology, protocols, and reagents described herein because they may vary. Further, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the present invention. As used herein and in the appended claims, the singular forms "a." "an.^" and "the" include plural reference unless the context clearly dictates otherwise. Similarly, the words '"comprise^"', "comprises'^", and '"comprising" are to be interpreted inclusively rather than exclusively.

[0060] Unless defined otherwise, all technical and scientific terms and any acronyms used herein have the same meanings as commonly understood by one of ordinary skill in the art in the field of the invention. Although any methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, the preferred methods, devices, and materials are described herein.

[0061 j All patents, patent applications, and publications mentioned herein are incorporated herein by reference to the extent allowed by law for the purpose of describing and disclosing the compounds, processes, techniques, procedures, technology, articles, and other compositions and methods disclosed therein that might be used with the present invention. However, nothing herein is to be construed as an admission that the invention is not entitled to antedate such disclosure by virtue of prior invention.

EXAMPLES

[0062] The invention can be further illustrated by the following examples of preferred embodiments thereof, although it will be understood that these examples are included merely for purposes of illustration and are not intended to limit the scope of the invention unless otherwise specifically indicated.

Example 1

[0063 J This example illustrates that levels of certain biomarkers. relative to reference levels, can be indicative of a body weight condition or predisposition in an animal. [0064] Twenty dogs (ten lean and ten obese) are used in a four day study to determine differences in serum metabolites between lean-prone and obese-prone dogs. Placement in the lean or obese group is determined by the following characteristics:

(a) propensity to gain weight (obese-prone) or to maintain weight (lean-prone) when fed ad libitum: (b) numerical body condition score ranging from I to 5 (lean-prone dogs have an average body condition score of about 3. whereas obese-prone dogs have an average body condition score of about 4.1 ): and

(c) past participation in weight loss studies (obese dogs have previous participation, whereas lean dogs have not).

[0065) Average body weight for lean-prone dogs is 12.06 kg and for obese-prone dogs 16.59 kg.

|0066] The dogs are fed, once daily for four days, a maintenance food formulated to meet or exceed nutritional requirements for maintenance of body weight (BW). On the fourth day. blood serum samples are taken prior to feeding (preprandial. time 0), and 10, 60. 120, and 360 minutes after feeding (postprandial). The samples are analyzed for insulin, triglycerides, glucose, GLP-K and ghrelin concentrations using standard procedures found, for example, in laboratory manuals such as Sambrook et al. (2001) Molecular Cloning: A Laboratory Manual, 3rd ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor. NY: Spector et al. (1998) Cells: A Laboratory Manual, Cold Spring Harbor Laboratory Press. Cold Spring Harbor, NY; and Hampton et al. (1990) Serological Methods: A Laboratory Manual, APS Press, Si Paul, MN. Serum concentrations of the biomarkers are adjusted for BW. Results are shown in Tables 1 through 5.

10067] Postprandial serum insulin concentrations do not differ substantially between lean- prone and obese-prone dogs (Table 1 ).

Table I Serum Insulin Levels

[0068] Also, serum triglyceride concentrations do not differ substantially between lean- prone and obese-prone dogs (Table 2). Table 2 Serum Triglyceride Levels

[0069J Serum concentrations of glucose (Table 3). GLP-I (Table 4), and ghrelin (Table 5) levels differ substantially between lean-prone and obese- prone dogs at most or all of the six sampling times.

Table 3 Serum Glucose Levels

Table 5 Serum Ghrelin Levels

[0070J Referring to the Tables, the data shows the utility of biomarkers. in particular serum glucose, GLP-I and ghrelin levels, to differentiate animals having lean and obese predisposition.

[0071] in the specification, there have been disclosed typical preferred embodiments of the invention and. although specific terms are employed, they are used in a generic and descriptive sense only and not for purposes of limitation, the scope of the invention being set forth in the claims. Obviously many modifications and variations of the invention are possible in light of the above teachings. It is therefore to be understood that within the scope of the appended claims the invention may be practiced otherwise than as specifically described.

Claims

What is claimed is:

1. A method for diagnosing a body weight condition or predisposition to a body weight condition in an animal comprising determining observed level(s) of at least one biomarker in a tissue or biofluid sample from the animal and comparing the observed level(s) to reference level(s) for the biomarker: wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition.

2. The method of Claim 1 wherein the animal is canine or feline.

3. The method of Claim 1 wherein the animal is up to about one year of age and the observed level(s) relative to the reference level(s) are individually or collectively indicative of predisposition to a body weight condition later in the animal^'s life.

4. The method of Claim 1 wherein the condition or predisposition is obesity or a propensity to gain weight.

5. The method of Claim 1 wherein the condition or predisposition increases the animal's risk for an overweight-related health disorder.

6. The method of Claim 5 wherein the ovenveight-related heath disorder is selected from the group consisting of hyperlipidemia. dyslipidemra, insulin resistance, glucose intolerance, hepatic lipidosis, anesthetic complications, hyperadrenocorticism. hypothyroidism, diabetes mellitus, insulinoma, pituitary chromophobe adenoma, hypopituitarism, hypothalamic lesions, joint stress, musculoskeletal pain, dyspnea, hypertension, dystocia, exercise intolerance, heat intolerance, decreased immune function, degenerative joint and orthopedic diseases, cardiovascular diseases, transitional cell carcinomas, fatigue, sleep disorders, reproductive disorders, and combinations thereof.

7. The method of Claim 1 wherein the biomarker is selected from the group consisting of glucose, GLP-I, ghrelin. and combinations thereof.

8. The method of Claim I wherein observed level(s) are determined for at least two biomarkers.

9. The method of Claim 1 wherein the tissue or biofluid sample is obtained when the animal is in a fasted state.

10. The method of Claim 1 wherein tissue or biofluid samples are obtained at a plurality of time points during a feeding cycle, including at least one preprandial time point and at least one postprandial time point.

1 1. The method of Claim 1 wherein the tissue or biofluid is whole blood, blood plasma or blood serum.

12. The method of Claim 1 wherein the observed and reference levels are determined using one or more assays independently selected from the group consisting of enzyme immunoassays, enzyme-linked immunosorbent assays, immunofluorescent assays, radioimmunoassays, western blot assays, biochemical assays, enzymatic assays, and colorimetric assays.

13. The method of Claim 1 wherein (a) the animal is canine, (b) the biomarker comprises glucose in serum, and (c) when the observed body weight-adjusted serum glucose level in a fasted animal is at least about 10% lower than the body weight-adjusted reference level for a canine of normal weight, a predisposition of the animal to gain weight is diagnosed.

14. The method of Claim 1 wherein (a) the animal is canine, (b) the biomarker comprises GLP-I in serum, and (c) when the observed body weight-adjusted serum GLP- I level in a fasted animal is at least about 20% lower than the body weight-adjusted reference level for a canine of normal weight, a predisposition of the animal to gain weight is diagnosed.

15. The method of Claim 1 wherein (a) the animal is canine, (b) the biomarker comprises ghrelin in serum, and (c) when the observed body weight-adjusted serum ghrelin level in a fasted animal is at least about 20% lower than the body weight-adjusted reference level for a canine of normal weight, a predisposition of the animal to gain weight is diagnosed.

16. A method for selecting a regimen for an animal comprising (a) diagnosing a body weight condition or predisposition by determining observed level(s) of at least one biomarker in a tissue or biofluid sample from the animal, and comparing the observed Ievel(s) to reference level(s) for the biomarker: wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition: and (b) identifying a regimen appropriate to the body weight condition or predisposition diagnosed.

17. The method of Claim 16 wherein the regimen comprises a composition for consumption by the animal.

18. The method of Claim 16 wherein the regimen comprises a form of exercise for the animal.

19. A method for detecting onset of a body weight condition or predisposition in an animal comprising monitoring at least one biomarker in the animal over a period by determining, at each of a plurality of time points during the period, observed level(s) of the biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker; wherein onset is detected if, at any time point, the observed level(s) relative to the reference level(s) are individually or collectively indicative of the body weight condition or predisposition.

20. The method of Claim 19 further comprising monitoring the animal's body weight by a technique selected from the group consisting of weighing, assessment of relative body weight, assessment of body condition score, morphometry, and combinations thereof.

21. A method for assessing the efficacy of a regimen for managing a body weight condition or predisposition in an animal comprising monitoring at least one biomarker in the animal over a period during which the regimen is administered, by determining, at each of a plurality of time points during the period, observed level(s) of the biomarker in a tissue or biofluid sample from the animal, and comparing the observed level(s) to reference level(s) for the biomarker; wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of the efficacy of the regimen in managing the body weight condition or predisposition.

22. A kit comprising:

(a) one or more reagents for detecting observed level(s) of at least one biomarker in a tissue or biofluid sample from an animal; and

(b) one or more user-accessible media carrying information that comprises (i) reference level(s) of the biomarker: and (ii) an algorithm that compares the observed level(s) to the reference level(s): wherein the observed level(s) relative to the reference level(s) are individually or collectively indicative of a body weight condition or predisposition in the animal.

23. The kit of Claim 22 wherein the one or more reagents comprise at least one reporter moiety or label.

24. The kit of Claim 22 wherein the one or more reagents comprise at least one antibody.

25. The kit of Claim 22 further comprising means for communicating information that comprises one or more of (a) a diagnosis of a body weight condition or predisposition as indicated by the observed level(s) relative to the reference levcl(s); and (b) a suggested or prescribed regimen appropriate to the diagnosis.