G蛋白偶联受体介导游离脂肪酸的信号通路及生理功能

Signal Pathway and Physiological Functions of Free Fatty Acids Mediated by G Protein-coupled Receptors

游离脂肪酸(free fatty acid,FFA)是动物一种重要能量来源,同时它还是一种重要的信号分子,其生理功能和作用机制长期以来倍受关注.最近研究表明,细胞膜存在FFA的特定孤儿型G蛋白偶联膜受体家族.中长链游离脂肪酸是GPR40和GPR120的配基,而短链游离脂肪酸则是GPR41和GPR43的配基.该受体家族可以介导游离脂肪酸,通过ERK、PI3K-Akt和MAPK信号通路,在维持机体内的葡萄糖稳态、脂肪形成、白细胞功能和细胞增殖等生理过程中发挥重要作用.本文就游离脂肪酸G蛋白偶联受体的结构、分布、配体选择性、下游信号通路,及其介导FFA生理功能的最新研究进展进行简要综述.

Free fatty acids（FFAs）,as important energy source for animals,are also key signal molecules whose physiological functions and mechanisms have drawn great attention for a long time.Recent studies have shown that several orphan G protein-coupled receptors（GPCRs） as membrane receptor for FFAs exist in cell membrane.The medium-long chain fatty acids are the ligands of GPR40 and GPR120,while short chain fatty acids are the ligands of GPR41and GPR43.These GPCRs for FFAs can mediate free fatty acids, and play a crucial role in maintaining glucose homeostasis, adipogenesis, leukocyte function and cell proliferation through ERK, PI3K-Akt and MAPK pathway. This article reviewed the structures, tissue distribution, ligand selectivity and downstream signal passage of GPCRs as well as the latest progress of the mediated physiological functions of FFAs.