脂肪酸受体4在食欲调控中的研究进展

Research advances of fatty acid receptor 4 in appetite control

食欲调控与人类健康密切相关。脂肪酸受体4(free fatty acid receptor 4,FFA4)具有重要的食欲调控功能,有望成为食欲调控药物的新靶点。中枢激活FFA4能够抑制神经肽Y(neuropeptide Y,NPY)神经元,缓解下丘脑炎症,提高中枢瘦素(leptin)和胰岛素(insulin)等抑食欲因子敏感性,从而发挥抑食欲作用。大量研究表明,FFA4在外周抑制食欲。一方面,FFA4与G_(i/o)蛋白偶联能够抑制腺苷酸环化酶途径,并抑制促食欲因子胃饥饿素(ghrelin)的表达,抑制食欲;另一方面,FFA4与G_(q11)蛋白激活下游的磷脂酰肌醇途径和PI3K/Akt途径,增加抑制食欲因子胰高血糖素样肽1(glucagon-like peptide 1,GLP-1)、胆囊收缩素(cholecystokinin,CCK)的分泌,抑制食欲。就FFA4对食欲调控作一综述,为以FFA4作为靶标开发食欲调控药物提供基础资料。

Appetite control is closely related to human health. Fatty acid receptor 4（FFA4） has an important appetite-regulating function and is expected to become a new target for appetite regulating drugs. Activation of FFA4 in the central nervous system can inhibit neuropeptide Y（NPY） neurons, relieve hypothalamic inflammation, and increase the sensitivity of central appetite factors such as leptin and insulin, thereby exerting appetite suppressant effects. The vast majority of studies have shown that FFA4 suppresses appetite in the periphery. On the one hand, FFA4 coupling with Gi/o protein can inhibit the adenylate cyclase pathway and inhibit the expression of the appetitive factor ghrelin and suppress appetite; on the other hand, FFA4 and Gq11 proteins activate the downstream phosphatidylinositol and PI3 K/Akt pathway. This pathway increases the secretion of the suppressor factors glucagon-like peptide 1（GLP-1） and cholecystokinin（CCK）, thereby suppressing appetite. This paper reviews the regulation of appetite by FFA4 in order to provide basic data for the development of appetite-regulating drugs with FFA4 as a target.