Branched chain amino acids and metabolic homeostasis regulation

Obesity and its induced diabetes and other metabolic diseases are in an outbreak trend in the world, so people pay more and more attention to the nutritional factors closely related to the occurrence of these diseases Amino acids, as the essential macro nutrients, have been widely known for their basic nutritional function and function In recent years, their nutritional regulation function has attracted much attention Guo Feifan, a researcher from the Institute of nutrition science, Shanghai Institute of life sciences, Chinese Academy of Sciences, reported the latest progress in the research field of amino acid and metabolic homeostasis regulation of his research group, under the title of "branched chain amino acid and metabolic homeostasis regulation", and clarified the important role and molecular mechanism of central nervous system in the process of amino acid nutrition induction and metabolic regulation When the essential amino acid leucine is deficient, the hormone sensitive lipase (HSL) mediated lipid mobilization in white adipose tissue (WAT) is enhanced, and the uncoupling protein 1 (UCP1) expression level in brown adipose tissue (BAT) is increased, heat production and energy consumption are increased, and the fat content is rapidly reduced In addition to amino acids related to the regulation of lipid energy homeostasis, leucine deficiency induced nutritional regulation signals through the activation of amino acid receptor Gcn2, amp activated protein kinase (AMPK) and so on, thus down regulating the activity of mammalian rapamycin target protein (mTOR) pathway and enhancing the sensitivity of insulin These results reveal the important functions of essential amino acids in regulating lipid energy metabolism and insulin sensitivity, confirm that Gcn2, AMPK and mTOR are regulated by amino acid nutrition, and are molecular targets for the development of drugs for the prevention and treatment of type 2 diabetes, and suggest that regulating amino acid level has the potential for the treatment of obesity and type 2 diabetes On this basis, the researchers studied the specificity of amino acid induced metabolic changes The deficiency of isoleucine and valine, which belong to branched chain amino acids, can increase the efficiency of fat mobilization and heat production of bat, inhibit mTOR, activate AMPK signaling pathway and enhance insulin sensitivity This suggests that there are some common regulatory mechanisms among different essential amino acids, energy and lipid metabolism and insulin sensitivity regulation, which lays a good foundation for the analysis of the regulatory mechanisms of different essential amino acids on energy and glucose and lipid metabolism, and is of great significance for guiding the public diet health ATF4 gene knockout increased fat synthesis inhibition, lipolysis ability and heat production efficiency in bat ATF4 gene deletion mice resisted fatty liver and insulin resistance induced by high sugar diet by changing the expression of SCD1 in liver; By regulating the expression of CYP2E1, we can regulate the oxidative stress induced by high-fat diet; by regulating pgc1a, we can participate in the process of cold stress regulation These studies show that ATF4 plays an important role in the regulation of amino acid sensing and glycolipid metabolism, and expands the physiological function and significance of ATF4 In addition, the researchers found that S6K and GS / Camp / PKA / CREB signal pathways in the hypothalamus induced leucine deficiency, activated the expression of corticotropin releasing hormone (CRH), further activated sympathetic nerve, and regulated lipid and energy metabolism These results elucidate the important role and molecular mechanism of central nervous system in the process of amino acid nutrition induction and metabolism regulation, and enrich the basic theory of central nervous system nutrition induction and energy lipid metabolism regulation.