Long noncoding RNA XIST regulates brown preadipocytes differentiation and combats high-fat diet induced obesity by targeting C/EBPα.
Long noncoding RNA XIST regulates brown preadipocytes differentiation and combats high-fat diet induced obesity by targeting C/EBPα.
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长非编码 RNA XIST 通过靶向 C/EBPα 调节棕色前脂肪细胞分化并对抗高脂肪饮食引起的肥胖
DOI：
10.1186/s10020-022-00434-3
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发表时间：
2022-01-21
期刊：
影响因子：
--
通讯作者：
Guan M
中科院分区：
文献类型：
--
作者：
Wu C;Fang S;Zhang H;Li X;Du Y;Zhang Y;Lin X;Wang L;Ma X;Xue Y;Guan M
背景棕色脂肪组织（BAT）的激活会增加能量消耗，这使其成为一种有吸引力的肥胖治疗策略。 LncRNA 在脂肪细胞分化和调节中发挥重要作用。在这里，我们评估了lncRNA XIST对棕色前脂肪细胞分化和代谢调节的影响。方法在人肾周（peri-N）和皮下脂肪组织（sub-Q）、棕色前脂肪细胞和3T3-L1前脂肪细胞中检测XIST表达水平。 XIST 过表达和敲低实验在棕色前脂肪细胞中进行。通过尾静脉注射质粒建立XIST过表达小鼠模型。结果在人脂肪组织中，雌性个体中XIST表达量显着高于雄性个体。在体外，XIST 表达在棕色脂肪细胞分化过程中显着上调。 XIST 敲低抑制棕色前脂肪细胞的分化，而 XIST 过表达则促进棕色前脂肪细胞完全分化。 RNA结合蛋白免疫沉淀（RIP）实验表明XIST可以直接与C/EBPα结合。在体内，XIST 过表达可预防高脂肪饮食诱导的肥胖并改善雄性小鼠的代谢紊乱。结论我们的结果表明，XIST 至少部分通过与转录因子 C/EBPα 结合来通过 BAT 激活来对抗肥胖。
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.
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影响因子：
12.3
作者：
Marchese FP;Raimondi I;Huarte M
通讯作者：
Huarte M
脂肪组织转录组的从头重建揭示了棕色脂肪细胞发育的长无编码RNA调节剂。
影响因子：
29
作者：
Alvarez-Dominguez JR;Bai Z;Xu D;Yuan B;Lo KA;Yoon MJ;Lim YC;Knoll M;Slavov N;Chen S;Peng C;Lodish HF;Sun L
通讯作者：
Sun L
影响因子：
5.4
作者：
Ikeda, Yoshito;Tsuchiya, Hiroyuki;Kogure, Kentaro
通讯作者：
Kogure, Kentaro
影响因子：
4.8
作者：
Hamm, JK;Park, BH;Farmer, SR
通讯作者：
Farmer, SR
影响因子：
15.9
作者：
Shimano, H;Shimomura, I;Horton, JD
通讯作者：
Horton, JD