FoxO1在糖脂代谢机制中的研究进展

Research progress of FoxO1 in the mechanisms of glucose and lipid metabolism

FoxO1是叉头转录家族O亚族的一类代谢性调节因子,通过磷酸化、乙酰化、泛素化修饰等方式调控多种基因的表达。FoxO1可以结合于PDX-1基因的启动子上,通过抑制其转录活性,抑制胰岛β细胞增殖、增加其去分化并促进其凋亡。同时,FoxO1还可以促进糖异生G6Pase和PEPCK基因的表达,增加胰岛素抵抗。此外,FoxO1还可以通过介导PPARγ转录而抑制脂肪发生,促进ApoC-Ⅲ的表达,升高血浆TG水平。FoxO1通路障碍可导致一些代谢性疾病的发生,包括糖尿病、肥胖和脂代谢紊乱等。本文就FoxO1对胰岛β细胞功能、胰岛素抵抗、肝脏葡萄糖生成及脂质代谢的影响进行综述。

FoxO1 is a metabolic regulator of the O subfamily in the forkhead transcription family, which regulates the expression of a variety of genes through phosphorylation, acetylation, and ubiquitination modification. FoxO1 can bind to the promoter of the PDX-1 gene, inhibiting its transcriptional activity, inhibiting the proliferation of pancreatic β cells, increasing their dedifferentiation and promoting their apoptosis. At the same time, FoxO1 can also promote the expression of gluconeogenic G6 Pase and PEPCK genes and increase insulin resistance. In addition, it can also mediate PPARγ transcription, inhibit lipogenesis, promote the expression of ApoC-Ⅲ and increase the level of plasma TG. The FoxO1 pathway abnormalities can lead to the occurrence of some metabolic diseases, including diabetes, obesity and lipid metabolism disorders. This article reviews the effects of FoxO1 on pancreatic β-cell function, liver glucose and lipid metabolism, adipose tissue, and FoxO1 signaling pathway related drugs.