College of Pharmacy, Chungnam National University, Daejeon 34134, the Republic of Korea.
Department of Pharmaceutical Research, KyongBo Pharmaceutical Co., Ltd, 174, Sirok-ro, Asan-si, Chungcheongnam-do 31501, the Republic of Korea.
Biomed Pharmacother. 2024 Jun;175:116735. doi: 10.1016/j.biopha.2024.116735. Epub 2024 May 13.
G-protein-coupled receptors are a diverse class of cell surface receptors that orchestrate numerous physiological functions. The G-protein-coupled receptors, GPR41 and GPR43, sense short-chain fatty acids (SCFAs), which are metabolites of dietary fermentation by the host's intestinal bacteria. These receptors have gained attention as potential therapeutic targets against various diseases because of their SCFA-mediated beneficial effects on the host's intestinal health. Mounting evidence has associated the activity of these receptors with chronic metabolic diseases, including obesity, diabetes, inflammation, and cardiovascular disease. However, despite intensive research using various strategies, including gene knockout (KO) mouse models, evidence about the precise roles of GPR41 and GPR43 in disease treatment remains inconsistent. Here, we comprehensively review the latest findings from functional studies of the signaling mechanisms that underlie the activities of GPR41 and GPR43, as well as highlight their multifaceted roles in health and disease. We anticipate that this knowledge will guide future research priorities and the development of effective therapeutic interventions.
G 蛋白偶联受体是一类多样化的细胞表面受体，它们协调着许多生理功能。G 蛋白偶联受体 GPR41 和 GPR43 感知短链脂肪酸（SCFAs），这些 SCFAs 是宿主肠道细菌通过饮食发酵产生的代谢物。由于它们介导的 SCFA 对宿主肠道健康的有益作用，这些受体已成为治疗各种疾病的潜在治疗靶点。越来越多的证据表明，这些受体的活性与慢性代谢性疾病有关，包括肥胖、糖尿病、炎症和心血管疾病。然而，尽管使用了包括基因敲除（KO）小鼠模型在内的各种策略进行了深入研究，但关于 GPR41 和 GPR43 在疾病治疗中的精确作用的证据仍然不一致。在这里，我们全面回顾了 GPR41 和 GPR43 活性相关信号机制的功能研究的最新发现，并强调了它们在健康和疾病中的多方面作用。我们预计，这些知识将指导未来的研究重点和有效的治疗干预措施的发展。
