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Starvation intervention method based on macro nutrient component change and mTOR signal inhibitor, and application thereof

A technology of inhibitors and nutrients, applied in the field of pharmacology, can solve problems such as weight loss failure and weight rebound, and achieve the effect of reducing body weight and body fat and improving metabolism

Pending Publication Date: 2021-06-25
SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, because dieting will activate the brain's hunger signal, the body has to interrupt the food restriction, resulting in weight rebound, and ultimately leading to weight loss failure
[0003] The main disadvantage of the most widely used dieting method at present is that the process of dieting will activate the brain's hunger signal pathway, so once you stop dieting, you will have hyperphagia and overeating, which will eventually lead to weight loss failure

Method used

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  • Starvation intervention method based on macro nutrient component change and mTOR signal inhibitor, and application thereof
  • Starvation intervention method based on macro nutrient component change and mTOR signal inhibitor, and application thereof
  • Starvation intervention method based on macro nutrient component change and mTOR signal inhibitor, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Embodiment 1 low-protein diet animal experiment

[0034]The low-protein diet treatment experiment was conducted with male mice C57BL / 6N. Ten specially designed foods were shared among the mice experiments. Among the ten kinds of specially designed foods, five kinds of foods are fixed in which the fat content is 60% (the ratio of energy), and the protein content is from 1% to 20%, specifically 1%, 2.5%, 5%, and 10% respectively. % and 20%, and the remaining energy is supplemented by carbohydrates, so the carbohydrate contents of these five foods are 39%, 37.5%, 35%, 30% and 20% respectively. The main components of carbohydrates are corn starch (Corn starch), maltodextrin (Maltodextrin 10) and sucrose (Sucrose), and the contents of sucrose and cellulose in all foods are respectively fixed at 5% of the total food energy. The fat content of the other five foods is 20%, and the protein content is the same as the above five foods, which are 1%, 2.5%, 5%, 10% and 20% respect...

Embodiment 2

[0043] Example 2 Correlation between low protein treatment and hypothalamus starvation pathway

[0044] In order to explore the effect of foods with different protein content on the gene expression signaling pathway in mouse hypothalamus, the present invention carried out transcriptome sequencing and analysis.

[0045] The present inventors conducted a general linear model analysis on the genes of the hunger signaling pathway, and treated mice with 10 kinds of food as described in Example 1 for 12 weeks, with the fat content in the food as a factor and the protein content as a covariate. The results showed that the four genes Pomc, Cartpt, Agrp and Npy in the starvation pathway were significantly correlated with the protein content in food (p=2.2×10 -4 , p=0.008, p=0.008 and p=8.77×10 -5 ). The specific change form is that the expression of Pomc and Cartpt in the low protein group (1%, 2.5% and 5%) is significantly reduced, while the expression of Agrp and Npy is significant...

Embodiment 3

[0046] Embodiment 3 Low protein treatment mice food intake significantly reduces

[0047] A previous study by the present inventors found that when mice were fed with food restriction after two weeks of food restriction and then fed back to normal food, they would consume less food than normal food (about 3.5g / day) Significantly increased (about 5g / day), therefore in order to explore whether 1% low-protein food processing mice also have retaliatory overeating behavior when feeding normal protein food, the following experiments were designed:

[0048] The standard diet of normal diet 20% protein 10% fat 70% carbohydrate was fed to the mice for a week, and then the mice were divided into 3 groups, wherein the first group was treated with a low-protein diet of 60% fat 1% protein 39% carbohydrate ( 1P), the second group of mice simulated the food intake of the 1% low-protein treatment group and gave the food of 60% fat 20% protein 20% carbohydrate (called 20% matching Feeding gro...

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Abstract

The invention relates to a starvation intervention method based on macro nutrient component change and an mTOR signal inhibitor, and an application thereof. Specifically disclosed is a method for inhibiting appetite, reducing hunger sensation, reducing body weight or body fat, and improving glucose tolerance, the method comprises administering an effective amount of the mTOR signaling pathway inhibitor to a subject or administering a low-protein diet to the subject, and the low-protein diet is that the protein content in macro nutrient components is less than 5% of the total energy. The method overcomes the technical prejudice, and accidentally finds that low-protein diet can reduce body weight and body fat and improve metabolism. In addition, it is found that the mouse subjected to low-protein food treatment lacks the phenotype of excessive diet after normal diet is recovered even under the condition that a re-starvation pathway is activated, and the phenomenon is related to the mTOR signal in the hypothalamus. By inhibiting the mTOR signal in the hypothalamus of the limited-feeding treatment mouse, the phenotype of lack of excessive feeding when 1% of low protein returns to normal diet can be simulated.

Description

technical field [0001] The invention belongs to the field of pharmacology, and in particular relates to a hunger intervention method and application based on changes in macronutrient components and mTOR signal inhibitors. Background technique [0002] The global prevalence of obesity is increasing rapidly. According to the World Health Organization, an estimated 1.9 billion adults worldwide were overweight in 2014, of whom at least 600 million were obese (World Health Organization, 2016 data). Obesity is a high risk factor for several noncommunicable diseases, including type 2 diabetes (T2D), cardiovascular disease, hypertension, dyslipidemia, and atherosclerosis. It is now widely accepted that obesity and overweight are the result of a surplus in net energy balance, that is, the body consumes more calories than the body expends. Therefore, reducing calorie intake (dieting) is one of the most commonly used weight loss methods at present. However, because dieting will acti...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P3/04A23L33/00
CPCA61K45/00A61P3/04A23L33/30
Inventor 约翰·罗杰·斯彼克曼乌英嘎
Owner SHENZHEN INST OF ADVANCED TECH CHINESE ACAD OF SCI
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