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

Hao Chen; Huabing Tan; Juan Wan; Yong Zeng; Jincheng Wang; Haichuan Wang; Xiaojie Lu

doi:10.1016/j.pharmthera.2023.108391

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

Pharmacol Ther. 2023 May:245:108391. doi: 10.1016/j.pharmthera.2023.108391. Epub 2023 Mar 22.

Authors

Hao Chen¹, Huabing Tan², Juan Wan³, Yong Zeng¹, Jincheng Wang⁴, Haichuan Wang⁵, Xiaojie Lu⁶

Affiliations

¹ Department of Liver Surgery and Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
² Department of Infectious Diseases, Liver Disease Laboratory, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
³ West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine / West China School of Nursing, Sichuan University, Chengdu, China.
⁴ Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
⁵ Department of Liver Surgery and Laboratory of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China; Department of Bioengineering and Therapeutic Sciences and Liver Center, University of California, San Francisco, CA, USA. Electronic address: haichuan.wang@scu.edu.cn.
⁶ Department of General Surgery, Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China. Electronic address: 189@whu.edu.cn.

PMID: 36963510
DOI: 10.1016/j.pharmthera.2023.108391

Abstract

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 γ (PPAR-γ), ligand-activated transcription factors of the nuclear hormone receptor superfamily, is considered a crucial metabolic regulator of hepatic lipid metabolism and inflammation. The role of PPAR-γ in the pathogenesis of NAFLD is gradually being recognized. Here, we outline the involvement of PPAR-γ in the pathogenesis of NAFLD through adipogenesis, insulin resistance, inflammation, oxidative stress, endoplasmic reticulum stress, and fibrosis. In addition, the evidence for PPAR-γ- targeted therapy for NAFLD are summarized. Altogether, PPAR-γ is a promising therapeutic target for NAFLD, and the development of drugs that can balance the beneficial and undesirable effects of PPAR-γ will bring new light to NAFLD patients.

Keywords: Adipogenesis; Fibrosis; Inflammation; NAFLD; PPAR-γ.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Humans
Inflammation / metabolism
Liver / metabolism
Non-alcoholic Fatty Liver Disease* / drug therapy
Non-alcoholic Fatty Liver Disease* / metabolism
PPAR gamma* / genetics
PPAR gamma* / metabolism
Signal Transduction

Substances

PPAR gamma