美国德克萨斯大学西南医学中心Da Young Oh和加州大学Jerrold M. Olefsky课题组合作取得一项新突破。他们发现G蛋白偶联受体120（GPR120）和PPARγ协同增强胰岛素敏感性的调控机制。这一研究成果在线发表在2020年5月14日出版的国际学术期刊《细胞-代谢》上。

研究人员发现PPARγ激动剂罗格列酮（Rosi）联合GPR120激动剂化合物A的疗法可产生累加效应，该方法在低剂量Rosi时可以改善葡萄糖耐受和胰岛素敏感性，并可避免Rosi已知的副作用。从机制上讲，研究发现GPR120是脂肪细胞中PPARγ的靶基因，GPR120则通过诱导内源性配体15d-PGJ2并阻断ERK介导的PPARγ抑制作用来增强PPARγ活性。此外，在巨噬细胞（MKO）或脂肪细胞特异性GPR120 敲除（AKO）的小鼠中，研究人员发现GRP120通过巨噬细胞发挥抗炎作用，同时与脂肪细胞中PPARγ协同作用可以增加胰岛素敏感性。这些结果为在临床上提高胰岛素敏感性提供了更安全的方法。

据悉，GPR120和PPARγ的激动剂均具有胰岛素增敏作用。但是，这两个途径是否在功能上相互作用并且可以一起使用以显著改善胰岛素抵抗尚未得到研究。

附：英文原文

Title: Positive Reinforcing Mechanisms between GPR120 and PPARγ Modulate Insulin Sensitivity

Author: Vivian A. Paschoal, Evelyn Walenta, Saswata Talukdar, Ariane R. Pessentheiner, Olivia Osborn, Nasun Hah, Tyler J. Chi, George L. Tye, Aaron M. Armando, Ronald M. Evans, Nai-Wen Chi, Oswald Quehenberger, Jerrold M. Olefsky, Da Young Oh

Issue&Volume: 2020-05-14

Abstract: G protein-coupled receptor 120 (GPR120) and PPARγ agonists each have insulin sensitizingeffects. But whether these two pathways functionally interact and can be leveragedtogether to markedly improve insulin resistance has not been explored. Here, we showthat treatment with the PPARγ agonist rosiglitazone (Rosi) plus the GPR120 agonistCompound A leads to additive effects to improve glucose tolerance and insulin sensitivity,but at lower doses of Rosi, thus avoiding its known side effects. Mechanistically,we show that GPR120 is a PPARγ target gene in adipocytes, while GPR120 augments PPARγactivity by inducing the endogenous ligand 15d-PGJ2 and by blocking ERK-mediated inhibitionof PPARγ. Further, we used macrophage- (MKO) or adipocyte-specific GPR120 KO (AKO)mice to show that GRP120 has anti-inflammatory effects via macrophages while workingwith PPARγ in adipocytes to increase insulin sensitivity. These results raise theprospect of a safer way to increase insulin sensitization in the clinic.

DOI: 10.1016/j.cmet.2020.04.020

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30237-0