Review Article

GPCRs involved in metabolic diseases: pharmacotherapeutic development updates

Cheng Jin1,2, Hui Chen1, Li Xie1, Yuan Zhou1, Li-li Liu3,4, Jian Wu1,3,4
1 Department of Medical Microbiology & Parasitology, MOE/NHC/CAMS Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University Shanghai Medical College, Shanghai 200032, China
2 College of Clinical Medicine, Fudan University Shanghai Medical College, Shanghai 200032, China
3 Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai 200032, China
4 Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai 200032, China
Correspondence to: Li-li Liu:, Jian Wu:,
DOI: 10.1038/s41401-023-01215-2
Received: 21 September 2023
Accepted: 11 December 2023
Advance online: 7 February 2024


G protein-coupled receptors (GPCRs) are expressed in a variety of cell types and tissues, and activation of GPCRs is involved in enormous metabolic pathways, including nutrient synthesis, transportation, storage or insulin sensitivity, etc. This review intends to summarize the regulation of metabolic homeostasis and mechanisms by a series of GPCRs, such as GPR91, GPR55, GPR119, GPR109a, GPR142, GPR40, GPR41, GPR43 and GPR120. With deep understanding of GPCR’s structure and signaling pathways, it is attempting to uncover the role of GPCRs in major metabolic diseases, including metabolic syndrome, diabetes, dyslipidemia and nonalcoholic steatohepatitis, for which the global prevalence has risen during last two decades. An extensive list of agonists and antagonists with their chemical structures in a nature of small molecular compounds for above-mentioned GPCRs is provided as pharmacologic candidates, and their preliminary data of preclinical studies are discussed. Moreover, their beneficial effects in correcting abnormalities of metabolic syndrome, diabetes and dyslipidemia are summarized when clinical trials have been undertaken. Thus, accumulating data suggest that these agonists or antagonists might become as new pharmacotherapeutic candidates for the treatment of metabolic diseases.
Keywords: G protein-coupled receptor; antagonist; agonist; diabetes; metabolic syndrome; nonalcoholic steatohepatitis

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