Long Noncoding RNA XIST Regulates Brown Preadipocytes Differentiation and Combats High-fat Diet Induced Obesity by Targeting C/EBPα

Overview

Journal Mol Med

Publisher Biomed Central

Specialties General Medicine
Molecular Biology

Date 2022 Jan 22

PMID 35062859

Authors

Chunyan Wu

Shu Fang

Huijian Zhang

Xiaoqiang Li

Yuejun Du

Yudan Zhang

Xiaochun Lin

Ling Wang

Xiaoqin Ma

Yaoming Xue

Meiping Guan

Affiliations

Soon will be listed here.

Abstract

Background: Activation of brown adipose tissue (BAT) increases energy expenditure, which makes it an attractive therapeutic strategy for obesity. LncRNAs play an important role in adipocyte differentiation and regulation. Here we assessed the effect of lncRNA XIST on brown preadipocytes differentiation and metabolic regulation.

Methods: XIST expression levels were detected in human perirenal (peri-N) and subcutaneous adipose tissues (sub-Q), brown preadipocytes and 3T3-L1 preadipocytes. XIST overexpression and knockdown experiments were performed in brown preadipocytes. XIST overexpression mouse model was established by plasmid injection through tail vein.

Results: In human adipose tissues, XIST expression was significantly higher in female than in male individuals. In vitro, XIST expression was significantly up-regulated during brown adipocyte differentiation. XIST knockdown inhibited differentiation of brown preadipocytes, while overexpression of XIST promotes brown preadipocytes to fully differentiation. RNA Binding Protein Immunoprecipitation (RIP) experiment revealed that XIST could directly bind to C/EBPα. In vivo, XIST overexpression prevents high-fat diet induced obesity and improves metabolic dysorder in male mice.

Conclusion: Our results suggest that XIST combats obesity through BAT activation at least partly by combination with transcription factor C/EBPα.

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