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GPCRs involved in metabolic diseases: pharmacotherapeutic development updates

Acta Pharmacologica Sinica (2024)Cite this article

Abstract

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.

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Fig. 1: Signaling pathways and metabolic effects GPCRs.
Fig. 2: Pharmacologic mechanisms of GPR55 antagonists in metabolic disorders.
Fig. 3: Promotional role of GPR142 agonists for potential treatment of type 2 diabetes.

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The authors declare that all the data supporting the findings of this study are contained within the paper.

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Funding

This manuscript is supported partially by the National Natural Science Foundation of China (NSFC #82370625, 82170624, 81871997, 81572356) and the National Key R&D Program of China (#2016YFE0107400) to J.W.

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  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

    Cheng Jin, Hui Chen, Li Xie, Yuan Zhou & Jian Wu

  2. College of Clinical Medicine, Fudan University Shanghai Medical College, Shanghai, 200032, China

    Cheng Jin

  3. Department of Gastroenterology & Hepatology, Zhongshan Hospital of Fudan University, Shanghai, 200032, China

    Li-li Liu & Jian Wu

  4. Shanghai Institute of Liver Diseases, Fudan University Shanghai Medical College, Shanghai, 200032, China

    Li-li Liu & Jian Wu

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  1. Cheng Jin
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Concept and literature review: JW, CJ, LLL. Manuscript preparation: CJ, HC, LX, YZ. Manuscript finalization: JW, LLL.

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Jin, C., Chen, H., Xie, L. et al. GPCRs involved in metabolic diseases: pharmacotherapeutic development updates. Acta Pharmacol Sin (2024). https://doi.org/10.1038/s41401-023-01215-2

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