氨基酸感应与糖脂代谢调控的研究进展

Research progress on amino acid sensing and its role in the regulation of glucose and lipid metabolism

氨基酸是机体必需的小分子代谢物,其作为信号分子广泛参与了对机体糖脂代谢稳态的维持和调控。研究表明,在糖脂能量代谢的调节过程中,支链氨基酸(尤其是亮氨酸)发挥了重要作用。机体与糖脂代谢相关的多个外周脏器(如肝脏、胰腺、白脂、褐脂、胃肠道等)和代谢调控中枢下丘脑均可以感应外界氨基酸水平的变化,并调节糖脂能量代谢。此外,氨基酸调节糖脂代谢的关键信号通路也已被广泛证实,如mTOR/S6K信号通路、GCN2/ATF4信号通路等。鉴于2型糖尿病等营养相关慢性代谢病的发病率不断攀升,对氨基酸的营养感应和糖脂代谢调控功能进行进一步探索将为代谢性疾病的防控提供重要的指导意义。

Amino acid is a type of micro-molecular metabolite essential for the maintenance of life. As a signal transducing molecule, amino acid extensively participates in the maintenance and regulation of glucose and lipid metabolism homeostasis. Previous research has confirmed the crucial role of amino acid, especially branched chain amino acid （BCAA; e.g., leucine） in the regulation of glucose/lipid and energy homeostasis. The metabolic control center hypothalamus, as well as multiple periphery organs correlated with glucose and lipid metabolism （such as liver, pancreas, white adipose tissue, brown adipose tissue, gastrointestinal tract） can sense the level of amino acid in external environment, and regulate glucose/lipid and energy metabolism. What is more, key signal transduction pathways affected by amino acid in the modulation of glucose and lipid metabolism have been well established, such as mTOR/S6K, GCN2/ATF4 pathway. In the view of constant increase of chronic metabolic diseases such as type 2 diabetes, further exploring on amino acid nutrient sensing and its metabolic control on glucose and lipid metabolism will provide significant guidance for the prevention and control of metabolic diseases.