NR4A1调控系统糖脂代谢的分子机制

NR4A1 regulates systemic glucose and lipid metabolism

系统性糖脂代谢紊乱是2型糖尿病、肥胖、非酒精性脂肪性肝病等代谢综合征的主要病理生理学改变。孤核受体家族成员NR4A1广泛表达于糖和脂质代谢旺盛的组织,例如:肝、脂肪和肌肉等组织,在不同组织或细胞中,NR4A1通过不同靶点,例如:AMPK、PPARγ、SREBP1c等参与机体糖脂代谢的调控。然而,NR4A1介导的系统糖脂代谢的调控机理目前仍存在很大争议,大部分研究认为NR4A1的表达具有降糖、降脂的作用,亦有研究认为NR4A1的表达促进脂肪生成。基于目前NR4A1参与机体糖脂代谢的研究,现对NR4A1在肝脏、脂肪和肌肉中参与葡萄糖和脂质代谢调控的分子机制进行总结。

Glucose and lipid metabolic disorders are the main pathophysiological changes of metabolic syndrome such as type 2 diabetes mellitus(T2DM), obesity, and nonalcoholic fatty liver disease(NAFLD). The orphan nucleus receptor NR4A1 is widely expressed in different organs or tissues such as liver, adipose tissue and muscle, where glucose and lipid are metabolized. In different tissues or cells, NR4A1 participates in the body’s glucose and lipids metabolism via different targets or molecules, such as AMPK, PPARγ, SREBP1c, etc. The regulation of NR4A1 on glucose and lipid metabolism is complex, leading to diverse and controversial conclusions. Most studies concluded that the expression of NR4A1 has the beneficial effect of reducing blood glucose and lipid, and some researchers found that the expression of NR4A1 promotes lipogenesis. Based on the current researches on NR4A1’s involvement in the metabolism of glucose and lipid in the body, this article retrospectively summarizes the involvement of NR4A1 in the regulation of glucose and lipid metabolism in liver, fat and muscle.