Long noncoding RNA XIST regulates brown preadipocytes differentiation and combats high-fat diet induced obesity by targeting C/EBP\u03b1

Chunyan Wu,Yuejun Du,Xiaoqin Ma,Huijian Zhang,Meiping Guan,Yaoming Xue,Xiaochun Lin,Xiaoqiang Li,Yudan Zhang,Ling Wang,Shu Fang

doi:10.1186/s10020-022-00434-3

Abstract

BackgroundActivation 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.MethodsXIST 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.ResultsIn 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.ConclusionOur results suggest that XIST combats obesity through BAT activation at least partly by combination with transcription factor C/EBPα.

Highlights

Adipose tissue plays an important role in metabolic homeostasis
Expression of X inactive-specific transcript (XIST) in human adipose tissues and mice adipocytes To explore whether lncRNA XIST is involved in the regulation of adipose tissue function, XIST was measured in adipose tissues
XIST expression was significantly higher in male subcutaneous adipose tissues than perirenal adipose tissues (Fig. 1A), which was inverse in female with no significance

Summary

Introduction

Adipose tissue plays an important role in metabolic homeostasis. Obesity is characterized by excessive accumulation of adipose tissue, leading to an increase risk of metabolic diseases (Blüher 2019). Men accumulate more visceral fat tissue, while premenopausal women accumulate more subcutaneous fat tissue (Palmer and Clegg 2015). These fat distribution pattern leads to typical women “Pear-shaped” obesity and male “apple-shaped” obesity (Gesta et al 2007). Previous studies suggest that lncRNA plays an important role in the differentiation of adipose tissue (Tran et al 2020; Xiao 2021). X inactive-specific transcript (XIST) lncRNA is the critical regulator in X-chromosome inactivation (Payer and Lee 2008), which play an important role in X–linked gene expression balance between. LncRNAs play an important role in adipocyte differentiation and regulation. We assessed the effect of lncRNA XIST on brown preadipocytes differentiation and metabolic regulation

Methods

Results

Conclusion