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长链非编码RNA Gm15290通过吸附微小RNA-27b来促进过氧化物酶体增殖物激活受体γ诱导的脂肪沉积,并导致小鼠体重增加。

LncRNA Gm15290 sponges miR-27b to promote PPARγ-induced fat deposition and contribute to body weight gain in mice.

作者信息

Liu Weihua, Ma Chunli, Yang Bin, Yin Chunyan, Zhang Beining, Xiao Yanfeng

机构信息

Pediatrics Department, The Second Affiliated Hospital of Xi'an Jiaotong University, China; Pediatrics Department, The First Hospital of Xi'an, China.

Pediatrics Department, Baoji People's Hospital, China.

出版信息

Biochem Biophys Res Commun. 2017 Nov 25;493(3):1168-1175. doi: 10.1016/j.bbrc.2017.09.114. Epub 2017 Sep 21.

Abstract

We found that Gm15290 was one of the most upregulated lncRNAs in the adipose of ob/ob mice through lncRNA microarray analysis. Then, manipulations of overexpression and silencing in mouse primary adipocytes showed that Gm15290 positively regulated adipogenesis, manifested by increasing lipid deposition and upregulating adipogenic genes including PPARγ, C/EBPα, and aP2. However, overexpression of mutant Gm15290 (at the binding site of miR-27c) did not have an promoting effect on adipogenesis. Additionally, Gm15290 was found to potentially interact with miR-27b that had been identified as a PPARγ targeting miRNA, and we verified their interaction by luciferase activity and RNA pull down assays. Furthermore, inhibition of Gm15290, by injection of the Gm15290 siRNA, decreased the body weight gain and mass of adipose tissues, including iWAT and eWAT, in mice fed with HFD. In conclusion, Gm15290 sponges miR-27b to increase fat deposition and body weight in HFD-fed mice.

摘要

通过lncRNA芯片分析,我们发现Gm15290是ob/ob小鼠脂肪组织中上调最为显著的lncRNAs之一。随后,在小鼠原代脂肪细胞中进行的过表达和沉默实验表明,Gm15290对脂肪生成具有正向调节作用,表现为脂质沉积增加以及包括PPARγ、C/EBPα和aP2在内的脂肪生成相关基因表达上调。然而,突变型Gm15290(在miR-27c的结合位点处)的过表达对脂肪生成并无促进作用。此外,我们发现Gm15290可能与已被鉴定为靶向PPARγ的miRNA的miR-27b相互作用,并通过荧光素酶活性和RNA下拉实验验证了它们之间的相互作用。进一步地,通过注射Gm15290 siRNA抑制Gm15290后,高脂饮食喂养小鼠的体重增加以及包括腹股沟白色脂肪组织和附睾白色脂肪组织在内的脂肪组织质量均有所降低。总之,在高脂饮食喂养的小鼠中,Gm15290通过吸附miR-27b增加脂肪沉积和体重。

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