College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.
Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Int J Mol Sci. 2021 Sep 23;22(19):10261. doi: 10.3390/ijms221910261.
Obesity has become a worldwide epidemic, caused by many factors such as genetic regulatory elements, unhealthy diet, and lack of exercise. MicroRNAs (miRNAs) are non-coding single-stranded RNA classes, which are about 22 nucleotides in length and highly conserved among species. In the last decade, a series of miRNAs were identified as therapeutic targets for obesity. In the present study, we found that miR-126b-5p was associated with adipogenesis. miR-126b-5p overexpression promoted the proliferation of 3T3-L1 preadipocytes by upregulating the expression of proliferation-related genes and downregulating the expression of apoptosis-related genes; the inhibition of miR-126b-5p gave rise to opposite results. Similarly, miR-126b-5p overexpression could promote the differentiation of 3T3-L1 preadipocytes by increasing the expression of lipid deposition genes and triglyceride (TG) and total cholesterol (TC) levels. Moreover, luciferase reporter assay demonstrated that adiponectin receptor 2 (Adipor2) and acyl-CoA dehydrogenase, long chain (ACADL) were the direct target genes of miR-126b-5p. Moreover, overexpression of miR-126b-5p could exacerbate the clinical symptoms of obesity when mice were induced by a high-fat diet, including increased adipose tissue weight, adipocyte volume, and insulin resistance. Interestingly, overexpression of miR-126b-5p in preadipocytes and mice could significantly increase total fatty acid content and change the fatty acid composition of adipose tissue. Taken together, the present study showed that miR-126b-5p promotes lipid deposition in vivo and in vitro, indicating that miR-126b-5p is a potential target for treating obesity.
肥胖已成为一种全球性的流行病，其病因有很多，包括遗传调控因子、不健康的饮食和缺乏运动等。微小 RNA（miRNA）是一类非编码的单链 RNA，长度约为 22 个核苷酸，在物种间高度保守。在过去的十年中，一系列 miRNA 被鉴定为肥胖的治疗靶点。在本研究中，我们发现 miR-126b-5p 与脂肪生成有关。miR-126b-5p 的过表达通过上调增殖相关基因的表达和下调凋亡相关基因的表达来促进 3T3-L1 前脂肪细胞的增殖；抑制 miR-126b-5p 则产生相反的结果。同样，miR-126b-5p 的过表达可以通过增加脂质沉积基因的表达以及甘油三酯（TG）和总胆固醇（TC）水平来促进 3T3-L1 前脂肪细胞的分化。此外，荧光素酶报告基因实验表明，脂联素受体 2（Adipor2）和长链酰基辅酶 A 脱氢酶（ACADL）是 miR-126b-5p 的直接靶基因。此外，当用高脂肪饮食诱导肥胖时，miR-126b-5p 的过表达会加重肥胖小鼠的临床症状，包括增加脂肪组织重量、脂肪细胞体积和胰岛素抵抗。有趣的是，miR-126b-5p 在脂肪细胞和小鼠中的过表达可以显著增加总脂肪酸含量并改变脂肪组织的脂肪酸组成。综上所述，本研究表明 miR-126b-5p 促进体内和体外的脂质沉积，提示 miR-126b-5p 是治疗肥胖的潜在靶点。
