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微小RNA-199a-3p通过靶向硬脂酰辅酶A去饱和酶影响脂肪细胞分化和脂肪酸组成。

miR-199a-3p affects adipocytes differentiation and fatty acid composition through targeting SCD.

作者信息

Tan Zhendong, Du Jingjing, Shen Linyuan, Liu Chendong, Ma Jideng, Bai Lin, Jiang Yanzhi, Tang Guoqing, Li Mingzhou, Li Xuewei, Zhang Shunhua, Zhu Li

机构信息

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

College of Life and Science, Sichuan Agricultural University, Chengdu 611130, China.

出版信息

Biochem Biophys Res Commun. 2017 Oct 7;492(1):82-88. doi: 10.1016/j.bbrc.2017.08.030. Epub 2017 Aug 10.

Abstract

Body fat mass is closely associated to diseases related to obesity. MicroRNAs (miRNAs, miR) are important regulatory molecules that function as post-transcriptional gene regulators of adipocyte development. In the current study, we revealed that reduced expression of miR-199a-3p in adipose tissue resulting from high fat diet (HFD)-induced obesity in mice. Overexpression of miR-199a-3p promoted adipocyte proliferation by regulating the expression of regulating factors of the cell cycle. Furthermore, miR-199a-3p blunted lipid accumulation in 3T3-L1 adipocytes. This was accompanied by a marked decrease in the expression of adipocyte-specific genes involved in lipogenic transcription, fatty acid synthesis, and fatty acid transportation. Furthermore, the fatty acid oxidation process was enhanced. Luciferase activity assays confirmed that miR-199a-3p regulates adipocyte differentiation by directly targeting the 3'-untranslated region (3'-UTR) of stearoyl-CoA desaturase (SCD). Moreover, miR-199a-3p regulates fatty acid composition by decreasing the ratio of unsaturated fatty acids (UFAs) in adipocytes transfected with miR-199a-3p mimics. These results suggest that miR-199a-3p may promote adipocyte proliferation, while also repressing adipocyte differentiation by down-regulating SCD and changing fatty acid composition during adipogenesis.

摘要

体脂量与肥胖相关疾病密切相关。微小RNA(miRNA,miR)是重要的调节分子,作为脂肪细胞发育的转录后基因调节因子发挥作用。在本研究中,我们发现高脂饮食(HFD)诱导的小鼠肥胖导致脂肪组织中miR-199a-3p表达降低。miR-199a-3p的过表达通过调节细胞周期调节因子的表达促进脂肪细胞增殖。此外,miR-199a-3p抑制3T3-L1脂肪细胞中的脂质积累。这伴随着参与脂肪生成转录、脂肪酸合成和脂肪酸转运的脂肪细胞特异性基因表达的显著降低。此外,脂肪酸氧化过程增强。荧光素酶活性测定证实,miR-199a-3p通过直接靶向硬脂酰辅酶A去饱和酶(SCD)的3'-非翻译区(3'-UTR)来调节脂肪细胞分化。此外,miR-199a-3p通过降低用miR-199a-3p模拟物转染的脂肪细胞中不饱和脂肪酸(UFA)的比例来调节脂肪酸组成。这些结果表明,miR-199a-3p可能促进脂肪细胞增殖,同时在脂肪生成过程中通过下调SCD和改变脂肪酸组成来抑制脂肪细胞分化。

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