核受体(nuclear receptors,NRs)是依赖配体激活的转录因子,经配体活化后参与众多物质调控,与多种疾病如代谢性疾病、炎症、癌症等密切相关.过氧化物酶体增殖物激活受体(peroxisome prolif-erator-activated receptors,PPARs)、法尼基衍生物X受体(farnesoid X receptor,FXR)和肝脏X受体(liver X receptor,LXR)是NRs家族重要成员,在调控肝脏脂肪合成、胆固醇代谢、脂肪酸氧化、炎症反应以及促纤维因子表达等过程发挥重要作用,成为非酒精性脂肪肝(nonalcoholic fatty liver disease,NAFLD)的治疗靶点.本文简要综述了PPARs、FXR和LXR在肝脏脂质代谢和炎症信号中的作用以及在NAFLD疾病中的调控机制、外源性配体和相互作用的研究进展,以期为NAFLD的治疗提供新思路.
The regulation and target of nuclear receptors PPAR,FXR and LXR in nonalcoholic fatty liver disease
Nuclear receptors(NRs),as ligand-dependent transcription factors,are involved in the regulation of many substances after ligand activation,and are closely related to many diseases such as metabolic diseases,inflammation,and cancer.Peroxisome proliferator-activated receptors(PPARs),farnesoid X receptor(FXR)and liver X receptor(LXR),as important members of the NRs family,play an important role in the regulation of liver fat synthesis,cholesterol metabolism,fatty acid oxidation,inflammatory response and the expression of fibrogenic factors.They have become therapeutic targets for nonalcoholic fatty liver disease(NAFLD).This paper briefly reviews the molecular roles of PPARs,FXR and LXR in liver lipid metabolism and inflammatory signals,as well as the regulatory mechanisms,exogenous ligands and interactions in NAFLD diseases,in order to provide new ideas for the treatment of NAFLD.
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