The Chinese Academy of Sciences reveals that Leucine deficiency can lead to central regulatory dysfunction.

In a new study, researchers from the Institute of Nutritional Sciences at the central nervous system have revealed the mechanism by which leucine deficiency regulates peripheral Lipid Metabolism, the paper was published online in Molecular Endocrinology, a well-known International Journal of Endocrinology. The research was led by Feifan Guo, a researcher at the Institute of Nutrition who received a doctorate in neurobiochemistry from the University of Tokyo in Japan in 2001 and later worked as a postdoctoral researcher in the United States, in 2007, he was recruited as a research fellow of the Institute of Nutritional Sciences at the Chinese Academy of Sciences, and was selected into the 100 person program. The work is supported by the Program 973, the Natural Science Foundation, the Shanghai Science and Technology Commission and the Chinese Academy of Sciences. The central nervous system pathway is closely related to the metabolic molecular regulatory network of peripheral tissues, and its dysfunction is an important cause of metabolic diseases. The central nervous system, especially the Hypothalamus, plays an important role in nutrient sensing and regulation of metabolism. The hypothalamus, which has dual functions of nerve and endocrine system, can directly sense the nutritional state of the body and activate the metabolic regulation of peripheral tissues through the nutrition sensing signal pathway. At present, there is no detailed report on the central nutritional induction of amino acids and its regulation on peripheral metabolism. LEUCINE is one of the body's Essential amino acid and an important metabolic regulator. Previous research by the team showed that leucine deficiency can cause extensive metabolic changes in the peripheral tissues of the body, these include liver Fatty acid synthesis suppression, increased insulin sensitivity, rapid fat loss in the abdomen, and increased heat production in Brown adipose tissue. It has also been found that leucine deficiency can cause changes in multiple signaling pathways in the Hypothalamus, it is suggested that the hypothalamus can respond to leucine deficiency and further regulate peripheral Lipid metabolism after a series of signal integration, but the specific mechanism is not clear. In this study, Dr. Cheng Ying and Zhang Qian of Guo's group found that mice fed leucine-deficient diets restored their hypothalamic leucine levels quickly after intracerebroventricular injection of leucine And can prevent leucine deficiency caused by the loss of white fat and Brown fat heat production increased phenotypic changes. Studies have shown that central injection of Leucine can change the phosphorylation level of hormone-sensitive Lipase (HSL) in white adipose tissue and the expression level of uncoupling protein 1(UCP1) in Brown adipose tissue. Further studies have shown that leucine deficiency leads to an increase in the expression of Corticotropin hormone (CRH) in the paraventricular nucleus of the Hypothalamus, which in turn activates sympathetic nervous system, on the one hand, it promoted the increase of Lipid in white adipose tissue, which showed the increase of phosphorylation level of HSL, on the other hand, it promoted the increase of energy consumption in Brown adipose tissue, which showed the increase of UCP1 EXPRESSION A combination of the two causes a rapid loss of abdominal fat. In vitro experiments, it was found that leucine lacked the GS/CAMP/PKA/CREB signal pathway to activate hypothalamic neurons, and Creb directly acts on the promoter region of CRH and regulates the expression of CRH. This study is the first to demonstrate that hypothalamic CRH is regulated by leucine levels and is a key regulator of peripheral lipid and energy metabolism induced by leucine deficiency. The results of this study have laid a solid foundation for the further study of central sensing amino acids and regulation of Peripheral Lipid metabolism, and enriched people's understanding of the regulation of peripheral metabolism by central nervous system, it is helpful to deepen the understanding of the mechanism of obesity and Related Metabolic Diseases