Astragalus polysaccharide regulates brown adipocytes differentiation by miR-6911 targeting Prdm16.
Astragalus polysaccharide regulates brown adipocytes differentiation by miR-6911 targeting Prdm16.
复制标题
DOI：
10.1002/lipd.12328
复制
发表时间：
2021-11
期刊：
影响因子：
1.9
通讯作者：
Shihe Zhang;Pengkang Song;Xiaoyou Chen;Yu Wang;Xuyang Gao;Lin Liang;Junxing Zhao
中科院分区：
文献类型：
--
作者：
Shihe Zhang;Pengkang Song;Xiaoyou Chen;Yu Wang;Xuyang Gao;Lin Liang;Junxing Zhao
棕色脂肪组织（BAT）是哺乳动物中与产热有关的特化组织。黄芪多糖（Astragalus polysaccharide，APS）是黄芪（Astragalus membranaceus）的主要天然活性成分，是世界上最受欢迎的中草药之一。APS在棕色脂肪细胞分化中的作用及其可能机制尚不清楚。本研究探讨了黄芪多糖对C3 H10 T1/2细胞向棕色脂肪细胞分化的影响。结果表明，黄芪多糖能促进棕色脂肪细胞分化，沿着提高胰岛素敏感性，并显著增加棕色脂肪形成标志蛋白（C/EBPα、C/EBPβ和PPARγ）、产热标志蛋白（UCP 1、PRDM 16和PGC-1α）和胰岛素敏感性标志蛋白（GLUT 4）的表达。同时，结果表明，胰岛素受体底物1（p-IRS 1）和磷酸化AKT（p-AKT）的磷酸化量增加，而IRS和AKT的总量没有改变，这两个是胰岛素信号通路中的关键因素。RNA-seq结果显示，APS改变了多种miRNA的表达谱，其中miR-6911作为一种通用调控因子的表达明显降低。重要的是，我们发现miR-6911通过靶向PR domain-containing 16（Prdm 16）调节棕色脂肪细胞的分化。此外，转染miR-6911模拟物后，与对照组和抑制剂组相比，PRDM 16蛋白表达显著降低，同时伴随着PPARγ、UCP 1和PGC-1α的降低。总的来说，我们的结果表明，APS通过靶向Prdm 16的miRNA-6911调节C3 H10 T 1/2细胞中棕色脂肪细胞的分化。
Brown adipose tissue (BAT) is a specialized tissue in mammals related to thermogenesis. The Astragalus polysaccharide (APS) is the major natural active component of Astragalus membranaceus, which has been recognized as one of the most popular herbal medicines worldwide. The role and possible mechanisms of APS on brown adipocytes differentiation is not well defined. Here, we explored the effect of APS on the differentiation of brown adipocytes in C3H10T 1/2 cells. The results showed that APS promoted the differentiation of brown adipocytes and improved insulin sensitivity along with significant increases in the expression of brown adipogenic marker proteins (C/EBPα, C/EBPβ, and PPARγ), thermogenesis marker proteins (UCP1, PRDM16, and PGC-1α), and insulin sensitivity marker protein (GLUT4). Meanwhile, the results showed that the amount of the phosphorylation of insulin receptor substrate 1 (p-IRS1) and phospho-AKT (p-AKT) which are critical factors in the insulin signaling pathway was increased without changing the total amount of IRS and AKT. Furthermore, the results of RNA-seq showed that APS altered the expression profiles of various miRNAs, and among which the expression of miR-6911 as a universal regulatory factor was significantly decreased. Importantly, we found that miR-6911 regulated the differentiation of brown adipocytes by targeting PR domain-containing 16 (Prdm16). In addition, after transfection of miR-6911 mimics, compared with the control and inhibitor group, PRDM16 protein expression significantly decreased, which was accompanied by the decrease of PPARγ, UCP1, and PGC-1α. Collectively, our results indicated that APS regulated brown adipocytes differentiation in C3H10T 1/2 cells via miRNA-6911 targeting Prdm16.