(Peer-Reviewed) GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis
Yan Chen ¹, Ying-na Xu ¹, Chen-yu Ye ¹, Wen-bo Feng ¹, Qing-tong Zhou 周庆同 ¹, De-hua Yang 杨德华 ² ³, Ming-wei Wang 王明伟 ¹ ² ³ ⁴
¹ Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China
中国 上海 复旦大学基础医学院药理学系
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
中国 上海 中国科学院上海药物研究所 受体结构与功能重点实验室 国家新药筛选中心
³ Research Center for Deepsea Bioresources, Sanya, 572025, China
中国 三亚 深海生物学研究室
⁴ School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China
中国 上海 上海科技大学生命科学与技术学院
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.
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