CN108542899A - Application of the α-ketoglutaric acid in terms of improving obese animal Thermogenesis and reducing body fat content - Google Patents
Application of the α-ketoglutaric acid in terms of improving obese animal Thermogenesis and reducing body fat content Download PDFInfo
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- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 title claims description 104
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 title claims description 51
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 title claims description 51
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/105—Aliphatic or alicyclic compounds
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/38—Other non-alcoholic beverages
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
The invention discloses application of the alpha Ketoglutarate in terms of improving obese animal body Thermogenesis and reducing body fat content.The present invention provides the new applications of alpha Ketoglutarate, alpha Ketoglutarate can significantly improve high fat diet animal body entirety heat production and brown fat heat production, the expression of brown fat heat production marker gene UCP1, PRDM16, PGC1 α, Cidea and Elovl3 can be significantly improved, in addition can also reduce the total body fat content of high fat diet animal body and different parts fat weight simultaneously.And, alpha Ketoglutarate is free of to animal or the harmful substance of human body, additive amount is few, it can be directly added into animal drinking water, feed, food or drug, have many advantages, such as safely, effectively, toxic side effect will not be caused, it has a extensive future in terms of improving the heat production of high fat diet animal and reducing body fat content, the treatment for obesity and relevant disease opens new approach.
Description
Technical field
The invention belongs to animal metabolism technical field, be related to α-ketoglutaric acid improve obese animal body Thermogenesis and
Reduce obese animal body fat content in terms of application, and in particular to α-ketoglutaric acid improve obese animal body entirety heat production and
Brown fat Thermogenesis, and reduce the total body fat content of obese animal body and different parts fat weight etc. are answered
With.
Background technology
For most of homeothermal animal, constant body temperature is maintained in various complex environments, needs efficient temperature
Spend regulating system.The constant equilibrium state derived from heat production and heat dissipation of body temperature.There are mainly four types of sides for origin of heat in animal body
Formula：Calorigenic action caused by basic metabolism, body activity, cold stimulation（Including shivering thermogenesis and nonshivering thermogenesis）And food
The fuel factor of object.When cold stimulation initial thermogenesis mechanism is to tremble, be heat is generated by trembling for musculature, but if
It is exposed in cold environment for a long time, then body temperature will be maintained by nonshivering thermogenesis.Brown adipose tissue（Brown
Adipose tissue, BAT）It is the main heating source of nonshivering thermogenesis, especially in the animal of newborn and hibernation
（Gesta etal.,2007）.Brown adipose tissue is a kind of fatty existence form for being different from white adipose, is different from white
The storage energy effect of fat, the major function of brown fat are to be used for heat production.In animal the total amount of BAT and distribution with species not
Same and animal different developmental phases and adaptive condition show different.Current research finds that white adipocyte is at certain
Under the conditions of a little（Such as：Cold, specific nutrition substance intake etc.）Brown can occur, form cream-coloured adipocyte（beige
adipocyte）.Cream-coloured adipocyte also has the function similar with brown fat cell, can promote body heat production.
Thermogenesis in Brown Adipose Tissue is mainly to be adjusted by central nervous system, the temperature sense that cold stimulation signal passes through body
Receiver is transmitted to brain and causes corresponding sympathetic nerve release neurotransmitters, to activate the uncoupling protein on mitochondrial inner membrane
（Uncoupling protein 1, UCP1）, so that the consumption of proton electrochemical potential energy is synthesized uncoupling with ATP, energy is with heat
Form discharges.In addition, specific nutrition substance（Such as resveratrol, capsaicine）Brown can also be activated by associated signal paths
The heat production of fat.When human body energy intake is excessive and energy expenditure is very few, extra energy will be stored in the form of fat
In body, obesity is caused in the course of time.Fat treatment and prevention are also concentrated mainly at 2 points：The intake of energy is reduced, is increased
Add the consumption of energy.The research for improving antiobesity agents before focuses on intake of the reduction to energy, there are also progress, but it is such
Improve fat drug and all lack complete effect and Adverse event assessment, causes drug application risk larger.
The modern life is constantly accelerated, and high fat diet is full of in people’s lives.High fat diet can make body be in sub- strong
Health higher load condition.And this influence does not induce single disease, and a kind of comprehensive effect makes the items of human body refer to
Mark deviates with normal value.It is high in fat to frequently can lead to a series of metabolism such as insulin resistance, diabetes and angiocardiopathy
The generation of disease.Therefore, there is an urgent need in the art to develop a kind of energy expenditure and Small side effects of capable of increasing can regulate and control to change
To the dysgenic potential drug of animal, this all has animal productiong and health important meaning for kind high fat diet.
Invention content
The technical problem to be solved by the present invention is to for above-mentioned existing promotion body heat production and raising energetic supersession scheme
Deficiency provides α-ketoglutaric acid and is improving obese animal body entirety heat production and brown fat heat production, and reduces obese animal
The application of the total body fat content of body and different parts fat weight etc., in the same of the application range for widening α-ketoglutaric acid
When, improve high fat diet or the fat harmful effect to animal.
The object of the present invention is to provide α-ketoglutaric acid as or prepare improve obese animal body Thermogenesis and/or
Reduce the application in the product of obese animal body fat content.
The purpose of the present invention is achieved by the following technical programs：
The result of study of the present invention shows that α-ketoglutaric acid can significantly improve the oxygen demand and quantity of heat production of high fat diet animal, carry
The rectal temperature of high high fat diet animal, improves the brown fat shell temperature of high fat diet animal, and significantly improves simultaneously
The mRNA and protein expression of brown fat heat production marker gene UCP1, PRDM16, PGC1 α, Cidea and Elovl3, in addition can also
Total body fat content of high fat diet animal is significantly reduced simultaneously, significantly reduces abdominal cavity fat weight and skin in high fat diet animal body
Lower fat weight.Therefore, α-ketoglutaric acid can improve body entirety Thermogenesis and while brown fat Thermogenesis,
Body fat content can be reduced, improves high fat diet or fat to animal harmful effect, obese animal body heat production is improved to prepare,
The drug and health products for reducing body fat content provide technical support.
Therefore, applying below should all be within protection scope of the present invention：
α-ketoglutaric acid as or prepare improve animal body Thermogenesis product in application.
α-ketoglutaric acid as or prepare improve animal brown fat heat production product in application.
α-ketoglutaric acid as or prepare improve animal brown fat heat production marker gene expression product in application.
Preferably, the brown fat heat production marker gene refers to UCP1, PRDM16, PGC1 α, Cidea or Elovl3.
α-ketoglutaric acid as or prepare improve animal body quantity of heat production, oxygen demand product in application.
α-ketoglutaric acid as or prepare reduce the total body fat content of animal product in application.
α-ketoglutaric acid as or prepare reduce animal body in abdominal cavity fat weight, subcutaneous fat weight product in
Using.
Preferably, the animal is high fat diet animal.The animal includes the animals such as people, mouse, pig, chicken, ox or sheep.
Preferably, the product is drug, food or health products etc..The definition of the food is：It can be edible or drinks
Substance, including processed food, semi-finished product and undressed food；Drinking water, beverage, food including the mankind etc., other animals
Drinking water, feed etc..
In addition, a kind of product for improving the heat production of animal brown fat and/or reducing the total body fat content of animal, includes
α-ketoglutaric acid, also within protection scope of the present invention.
Preferably, the animal is high fat diet animal.The animal includes the animals such as people, mouse, pig, chicken, ox or sheep.
Preferably, the product is drug, food or health products etc..
Preferably, α-ketoglutaric acid can be directly appended in animal foodstuff by the present invention, the additive amount of α-ketoglutaric acid
It is the 0.1%~4% of animal foodstuff total weight.
Case study on implementation as one preferred, the present invention are by α-ketoglutaric acid and carrier（Preferred vector is diatomite, stone
Powder or stearic acid）In mass ratio 1:After 1~5 compounding, then compound is added in animal feed, the additive amount of compound is
The 0.1%~4% of object feed total weight.
It is highly preferred that the mass percentage of the α-ketoglutaric acid is 2%.
Compared with prior art, the beneficial effects of the invention are as follows：
The present invention by test prove, added in animal feed or drinking water a small amount of α-ketoglutaric acid can significantly improve it is high in fat
Diet animal body entirety heat production and brown fat heat production, while reducing the total body fat content of high fat diet animal and reducing different portions
Position fat weight, the treatment for obesity and relevant disease open new approach.
α-ketoglutaric acid of the present invention is animal body metabolic intermediate, without to animal or the harmful object of human body
Matter, safety and easily acquisition, additive amount is less, can be directly added into animal drinking water, feed, food or drug, the life of performance
Reason activity is high, have many advantages, such as conveniently, safely, effectively, toxic side effect will not be caused, improving obese animal heat production and reduction body
There is good popularizing application prospect in terms of fat content.
Description of the drawings
Fig. 1 is that drinking-water 2% α-ketoglutaric acid of addition feeds mouse body entirety oxygen demand and quantity of heat production, body to diet high in fat
The influence of temperature and brown fat heat production.
Fig. 2 is that drinking-water 2% α-ketoglutaric acid of addition feeds mouse body fat content and different parts fat weight to diet high in fat
The influence of amount.
Fig. 3 is drinking-water 2% α-ketoglutaric acid of addition to diet high in fat feeding mouse brown fat heat production marker gene expression
Influence.
Specific implementation mode
It is further illustrated the present invention below in conjunction with Figure of description and specific embodiment, but embodiment is not to the present invention
It limits in any form.Unless stated otherwise, the present invention uses reagent, method and apparatus routinely try for the art
Agent, method and apparatus.
Unless stated otherwise, following embodiment agents useful for same and material are purchased in market.
Diet feeding mouse body oxygen consumption and Thermogenesis high in fat can be improved in 1 α-ketoglutaric acid of embodiment
1, it is research α-ketoglutaric acid（AKG）The influence of mouse body oxygen consumption and Thermogenesis, experiment are fed to diet high in fat
Using the female C57BL/6 mouse of 10 week old as research object.
2, experimental method
（1）Animal feeding condition：1/case, monoculture；Raising temperature and humidity：20~26 DEG C, 40%~70%；Using 12 h：12
H intermittent illuminations round the clock；Receptacle condition remains stable, with the reliability of guarantee test result.Ad lib is drunk water, feed
It is provided by Guangdong Medical Lab Animal Center with drinking water；Quarantine：7 d are raised in advance to buying SPF grades of C57BL/6 J mouse.
Period daily check animal is primary.
（2）Animal packet and processing：20 10 week old female C57BL/6J mouse stochastic averaginas are divided into high in fat group and height
Fat+α-ketoglutaric acid group, every group of 10 mouse.High in fat group of mouse only feeds diet high in fat；High in fat+α-ketoglutaric acid is high except feeding
Outside fat diet, while 2% α-ketoglutaric acid is added in drinking-water.
（3）Metabolic cage experiment, the oxygen demand in 24 h of detection mouse and heat production situation are carried out when experiment proceeds to the 20th week.
Further to study influence of the α-ketoglutaric acid to mouse brown fat heat production, when experiment proceeds to the 11st week,
Mouse body surface picture is shot with thermal imaging instrument under normal temperature state, counts the shell temperature of its inter-scapular region brown fat.
Then cold stimulation 4 hours at 4 DEG C, reusable heat Image-forming instrument shoot mouse body surface picture, count mouse inter-scapular region brown
The shell temperature of fat.
3, the results are shown in Figure 1：
（1）Metabolic cage experiment, the oxygen demand in 24 h of detection mouse and heat production situation are carried out when experiment proceeds to the 20th week.As a result
As shown in Figure 1A and 1B, compared with high in fat group, either daytime or night, drinking-water 2% α-ketoglutaric acid of addition can be notable
Improve the oxygen demand and quantity of heat production of diet feeding mouse high in fat.
（2）In addition, as shown in Figure 1 C, compared with high in fat group, 2% α-ketoglutaric acid of drinking-water addition is remarkably improved feeding high in fat
Grain feeds the rectal temperature of mouse.
（3）As shown in figure iD, compared with high in fat group, drinking-water adds the shell temperature result of mouse inter-scapular region brown fat
2% α-ketoglutaric acid is added to be remarkably improved the brown fat shell temperature of diet feeding mouse high in fat.
It is above-mentioned the experiment results show that 2% α-ketoglutaric acid of addition is remarkably improved the body consumption of diet high in fat feeding mouse
Oxygen amount and Thermogenesis.
2 drinking water of embodiment, which adds 2% α-ketoglutaric acid, reduces diet feeding mouse body fat content high in fat
1, the influence for research α-ketoglutaric acid to feeding mouse body fat content high in fat, is tested with the female C57BL/6 of 10 week old
Mouse is research object.
2, experimental method
（1）Veterinary method：With embodiment 1.
（2）Animal packet and processing：With embodiment 1.
（3）Sampling and detection：Body composition and body imaging test are carried out when experiment carries out the 8th week.
3, the results are shown in Figure 2：
（1）As a result as shown in attached drawing 2A and 2B, compared with high in fat group, 2% α-ketoglutaric acid of drinking-water addition can significantly reduce high in fat
Diet feeds total body fat content of mouse.
（2）When experiment proceeds to the 20th week, the abdominal cavity fat and subcutaneous fat weight weighed in Mice Body are sampled.As a result such as
Shown in attached drawing 2C, compared with high in fat group, 2% α-ketoglutaric acid of drinking-water addition can significantly reduce abdomen in diet feeding Mice Body high in fat
Chamber fat and subcutaneous fat weight（Percentage of liveweight ratio）.
It is above-mentioned the experiment results show that 2% α-ketoglutaric acid of addition can significantly reduce total body fat of diet high in fat feeding mouse
The weight of content and subcutaneous fat and inherent fat, to which effectively prevention is fat.
3 drinking water of embodiment, which adds 2% α-ketoglutaric acid, can improve diet feeding mouse brown fat heat production energy high in fat
Power
1, the influence for research α-ketoglutaric acid to feeding mouse brown fat Thermogenesis high in fat, is tested with the female of 10 week old
C57BL/6 mouse are research object.
2, experimental method
（1）Veterinary method：With embodiment 1.
（2）Animal packet and processing：With embodiment 1.
（3）Sampling and detection：In order to further study α-ketoglutaric acid to heat production gene expression in mouse brown fat
It influences, we acquire the brown adipose tissue of mouse, and have detected the albumen table of associated heat generation gene in mouse brown fat
It is expressed up to mRNA.
3, the results are shown in Figure 3：
（1）As shown in figs.3 a and 3b, compared with high in fat group, drinking water adds 2% α-ketoglutaric acid and is remarkably improved diet high in fat
Feed the protein expression of mouse brown fat heat production marker gene UCP1, PRDM16, PDH and Cyto C（Fig. 3 A）, while can show
Write the mRNA expression for improving brown fat heat production marker gene UCP1, PRDM16, PGC1 α, Cidea and Elovl3（Fig. 3 B）.
It is above-mentioned to promote the expression of brown fat heat production marker gene the experiment results show that adding 2% α-ketoglutaric acid and pass through
Mouse brown fat Thermogenesis is fed to improve diet high in fat.
Claims (10)
1. α-ketoglutaric acid as or prepare improve animal body Thermogenesis product in application.
2. α-ketoglutaric acid as or prepare improve animal brown fat heat production product in application.
3. α-ketoglutaric acid as or prepare improve animal brown fat heat production marker gene expression product in application.
4. application according to claim 3, which is characterized in that the brown fat heat production marker gene refer to UCP1,
PRDM16, PGC1 α, Cidea or Elovl3.
5. α-ketoglutaric acid as or prepare improve animal body quantity of heat production, oxygen demand product in application.
6. α-ketoglutaric acid as or prepare reduce the total body fat content of animal product in application.
7. α-ketoglutaric acid as or prepare reduce animal body in abdominal cavity fat weight, subcutaneous fat weight product in answering
With.
8. according to any application of claims 1 to 3 or 5~7, which is characterized in that the animal is high fat diet animal.
9. a kind of product for improving the heat production of animal brown fat and/or reducing the total body fat content of animal, which is characterized in that packet
Contain α-ketoglutaric acid.
10. product according to claim 9, which is characterized in that the animal is high fat diet animal.
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| CN115836710A (en) * | 2022-12-15 | 2023-03-24 | 黑龙江八一农垦大学 | Composite preparation for improving animal reproductive performance and application |
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