Review Article

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis

Yan Chen1, Ying-na Xu1, Chen-yu Ye1, Wen-bo Feng1, Qing-tong Zhou1, De-hua Yang2,3, Ming-wei Wang1,2,3,4
1 Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2 The CAS Key Laboratory of Receptor Research and The National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
3 Research Center for Deepsea Bioresources, Sanya 572025, China
4 School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China
Correspondence to: De-hua Yang: dhyang@simm.ac.cn, Ming-wei Wang: mwwang@simm.ac.cn,
DOI: 10.1038/s41401-021-00836-9
Received: 10 June 2021
Accepted: 29 November 2021
Advance online: 21 December 2021

Abstract

Nonalcoholic steatohepatitis (NASH), as a severe form of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis. The pathogenesis of NASH is complex and multifactorial, obesity and type 2 diabetes mellitus (T2DM) have been implicated as major risk factors. Glucagon-like peptide-1 receptor (GLP-1R) is one of the most successful drug targets of T2DM and obesity, and its peptidic ligands have been proposed as potential therapeutic agents for NASH. In this article we provide an overview of the pathophysiology and management of NASH, with a special focus on the pharmacological effects and possible mechanisms of GLP-1 mimetics in treating NAFLD/NASH, including dual and triple agonists at GLP-1R, glucose-dependent insulinotropic polypeptide receptor or glucagon receptor.
Keywords: NAFLD; NASH; GLP-1R; GLP-1 mimetics; dual agonists; triple agonists; GPCR

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