PPAR-? signaling in nonalcoholic fatty liver disease: Pathogenesis and therapeutic targets

Non-alcoholic fatty liver disease (NAFLD), currently the leading cause of global chronic liver disease, has emerged as a major public health problem, more efficient therapeutics of which are thus urgently needed. Peroxisome proliferator-activated receptor gamma (PPAR-gamma), ligand-activated transcription factors of the nuclear hormone recep-tor superfamily, is considered a crucial metabolic regulator of hepatic lipid metabolism and inflammation. The role of PPAR-gamma in the pathogenesis of NAFLD is gradually being recognized. Here, we outline the involvement of PPAR-gamma in the pathogenesis of NAFLD through adipogenesis, insulin resistance, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. In addition, the evidence for PPAR-gamma-targeted therapy for NAFLD are summarized. Altogether, PPAR-gamma is a promising therapeutic target for NAFLD, and the development of drugs that can balance the beneficial and undesirable effects of PPAR-gamma will bring new light to NAFLD patients.(c) 2023 Elsevier Inc. All rights reserved.