GPR41 and GPR43 in Obesity and Inflammation - Protective or Causative?
GPR41 and GPR43 in Obesity and Inflammation - Protective or Causative?
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DOI：
10.3389/fimmu.2016.00028
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发表时间：
2016
影响因子：
7.3
通讯作者：
Ding JL
中科院分区：
文献类型：
--
作者：
Ang Z;Ding JL
GPR 41和GPR 43是一对在人脂肪细胞、结肠上皮细胞和外周血单核细胞中表达的哺乳动物G蛋白偶联受体（GPCR）。这些受体被短链脂肪酸（SCFA）激活，如乙酸酯，丙酸酯和丁酸酯-它们是由肠道细菌在膳食纤维发酵过程中产生的。这种独特的配体特异性表明，GPR 41和GPR 43可能介导人类宿主与肠道微生物组之间的相互作用。事实上，对基因敲除小鼠的研究表明，GPR 41和GPR 43与慢性炎症性疾病如肥胖、结肠炎、哮喘和关节炎有关。然而，GPR 41和GPR 43是保护性的还是致病性的，在研究之间并不一致。这种差异可能是由于所用疾病模型、近交系小鼠品系或非特异性敲除效应的差异。在这里，我们回顾了关于GPR 41和GPR 43的最新发现，强调了相互矛盾的观察结果。由于GPR 41和GPR 43被认为是药物靶标，因此充分阐明它们的作用是相关的。我们建议，未来对人体组织的体外研究可能使我们能够确认GPR 41和GPR 43在人体中的作用，无论是保护性的还是致病性的。
GPR41 and GPR43 are a pair of mammalian G protein-coupled receptors (GPCRs) expressed in human adipocytes, colon epithelial cells, and peripheral blood mononuclear cells. These receptors are activated by short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate – which are produced during dietary fiber fermentation by resident gut bacteria. This unique ligand specificity suggests that GPR41 and GPR43 may mediate the interaction between the human host and the gut microbiome. Indeed, studies on knockout mice implicate GPR41 and GPR43 in chronic inflammatory disorders such as obesity, colitis, asthma and arthritis. However, whether GPR41 and GPR43 are protective or causative is inconsistent between studies. This discrepancy may be due to differences in the disease models used, the inbred mouse strains, or non-specific knockout effects. Here, we review the latest findings on GPR41 and GPR43, highlighting contradictory observations. With GPR41 and GPR43 being considered as drug targets, it is pertinent that their role is fully elucidated. We propose that future studies on human tissues, ex vivo, may allow us to confirm the role of GPR41 and GPR43 in humans, be it protective or causative.