[脂联素-1在酒精性脂肪性肝病发病机制中的作用]

[Role of lipin-1 in the pathogenesis of alcoholic fatty liver disease].

作者信息

Li Y Y, Zhou J Y

机构信息

Department of Infectious Disease, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2016 Mar 20;24(3):237-40. doi: 10.3760/cma.j.issn.1007-3418.2016.03.017.

DOI:10.3760/cma.j.issn.1007-3418.2016.03.017

PMID:27095772

Abstract

Lipin-1 can promote the synthesis of triglyceride and fatty acid oxidation during lipid metabolism. Ethanol can up-regulate the expression of lipin-1 via the AMPK-SREBP-1-lipin-1 signaling pathway and increase lipin1β/αratio via the SITR1-SFRS10-LPIN1 signaling pathway. In the cytoplasm, lipin-1βfunctions as a Mg2+-dependent phosphatidic acid phosphohydrolase to accelerate the synthesis of triglyceride. In the nucleus, lipin-1αacts as a transcriptional coactivator and reduces mitochondrial fatty acid oxidation by inhibiting the activities of PPARαand PGC-1α, and therefore promotes lipid deposition in hepatocytes and causes hepatic steatosis.

摘要

脂联素-1在脂质代谢过程中可促进甘油三酯的合成及脂肪酸氧化。乙醇可通过AMPK-SREBP-1-脂联素-1信号通路上调脂联素-1的表达，并通过SITR1-SFRS10-LPIN1信号通路增加脂联素1β/α的比例。在细胞质中，脂联素-1β作为一种依赖Mg2+的磷脂酸磷酸水解酶，加速甘油三酯的合成。在细胞核中，脂联素-1α作为一种转录共激活因子，通过抑制PPARα和PGC-1α的活性来减少线粒体脂肪酸氧化，从而促进肝细胞中的脂质沉积并导致肝脂肪变性。