Song Tongxing, Zhou Yuanfei, Peng Jian, Tao Ya-Xiong, Yang Yang, Xu Tao, Peng Jie, Ren Jiao, Xiang Quanhang, Wei Hongkui
Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China.
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, AL, 36849, USA.
Mol Cell Endocrinol. 2016 Oct 15;434:1-13. doi: 10.1016/j.mce.2016.06.009. Epub 2016 Jun 11.
Numerous researches have demonstrated that GPR120 (also called FFAR4) exerts novel functions in insulin resistance and adipogenesis. However, the molecular mechanism of GPR120-mediated adipogenic differentiation is still unclear. This study was aimed to interpret the relevant function mechanism of GPR120 in the differentiation of 3T3-L1 adipocytes. The results showed that GPR120 expression was dramatically increased along with the adipogenic differentiation of 3T3-L1 adipocytes and the adipogenic ability was significantly inhibited in shGPR120-transfected cells. TUG-891, a selective agonist of GPR120, promoted the intracellular triglyceride accumulation in a dose-dependent manner and did not enhance adipogenesis in shGPR120-transfected cells. Markedly, TUG-891 increased the activation of PPARγ in a GPR120-dependent pathway as assessed by luciferase reporter assay. Furthermore, in the adipogenic differentiation process of 3T3-L1 adipocytes, TUG-891 increased the [Ca(2+)]i and phosphorylation level of ERK1/2. Pretreatment with inhibitors of either ERK1/2 (U0126) or [Ca(2+)]i (BAPTA-AM) notably attenuated the GPR120-mediated adipogenesis. These results show that GPR120 promotes adipogenesis by increasing PPARγ expression via [Ca(2+)]i and ERK1/2 signal pathway in 3T3-L1 adipocytes.
众多研究表明，GPR120（也称为FFAR4）在胰岛素抵抗和脂肪生成中发挥着新功能。然而，GPR120介导的脂肪生成分化的分子机制仍不清楚。本研究旨在阐释GPR120在3T3-L1脂肪细胞分化中的相关功能机制。结果显示，随着3T3-L1脂肪细胞的脂肪生成分化，GPR120表达显著增加，并且在转染shGPR120的细胞中脂肪生成能力受到显著抑制。GPR120的选择性激动剂TUG-891以剂量依赖的方式促进细胞内甘油三酯积累，并且在转染shGPR120的细胞中不增强脂肪生成。值得注意的是，通过荧光素酶报告基因检测评估，TUG-891在GPR120依赖的途径中增加了PPARγ的激活。此外，在3T3-L1脂肪细胞的脂肪生成分化过程中，TUG-891增加了细胞内钙离子浓度（[Ca(2+)]i）和ERK1/2的磷酸化水平。用ERK1/2抑制剂（U0126）或[Ca(2+)]i抑制剂（BAPTA-AM）预处理显著减弱了GPR120介导的脂肪生成。这些结果表明，GPR120通过[Ca(2+)]i和ERK1/2信号通路增加PPARγ表达来促进3T3-L1脂肪细胞的脂肪生成。
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