Hepatic lipid homeostasis by peroxisome proliferator-activated receptor gamma 2 ^☆

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ or PPARG) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. It plays a master role in the differentiation and proliferation of adipose tissues. It has two major isoforms, PPARγ1 and PPARγ2, encoded from a single gene using two separate promoters and alternative splicing. Among them, PPARγ2 is most abundantly expressed in adipocytes and plays major adipogenic and lipogenic roles in the tissue. Furthermore, it has been shown that PPARγ2 is also expressed in the liver, specifically in hepatocytes, and its expression level positively correlates with fat accumulation induced by pathological conditions such as obesity and diabetes. Knockout of the hepatic Pparg gene ameliorates hepatic steatosis induced by diet or genetic manipulations. Transcriptional activation of Pparg in the liver induces the adipogenic program to store fatty acids in lipid droplets as observed in adipocytes. Understanding how the hepatic Pparg gene expression is regulated will help develop preventative and therapeutic treatments for non-alcoholic fatty liver disease (NAFLD). Due to the potential adverse effect of hepatic Pparg gene deletion on peripheral tissue functions, therapeutic interventions that target PPARγ for fatty liver diseases require fine-tuning of this gene’s expression and transcriptional activity.