Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, China.
Gene. 2020 Mar 10;730:144260. doi: 10.1016/j.gene.2019.144260. Epub 2019 Nov 21.
Adipocyte differentiation, which plays an important role in the development of obesity, involves complex molecular networks in which microRNAs (miRNAs) are essential. Here, we show that miR-9 expression was upregulated during adipogenesis in 3T3-L1 cells. miR-9 overexpression reduced the accumulation of lipid droplets and the content of triglycerides by downregulating patatin-like phospholipase domain-containing protein 3 (PNPLA3). PNPLA3 knockdown or miR-9 overexpression downregulated the protein expression of peroxisome proliferator-activated receptor γ, oxidative tissue-enrichedPAT, and LC3, and promoted the phosphorylation of AMP-activated protein kinase (AMPK), which was inhibited by treatment with the AMPK inhibitor compound C. These results indicate that miR-9 inhibits adipocyte differentiation by targeting PNPLA3 through the AMPK pathway.
脂肪细胞分化在肥胖的发生发展中起着重要作用,涉及到 miRNA(microRNAs)等多种分子网络的参与,miRNA 在其中发挥着关键作用。在这里,我们发现 miR-9 在 3T3-L1 细胞的脂肪生成过程中表达上调。miR-9 过表达通过下调 patatin 样磷脂酶结构域包含蛋白 3(PNPLA3)减少了脂滴的积累和甘油三酯的含量。PNPLA3 敲低或 miR-9 过表达下调过氧化物酶体增殖物激活受体 γ、氧化组织丰富的 PAT 和 LC3 的蛋白表达,并促进 AMP 激活蛋白激酶(AMPK)的磷酸化,而 AMPK 抑制剂复合物 C 的处理抑制了这一过程。这些结果表明,miR-9 通过 AMPK 通路靶向 PNPLA3 抑制脂肪细胞分化。