Key result
Overexpression of lncRNA XIST promoted brown preadipocyte differentiation and prevented high-fat diet-induced weight gain in male mice by targeting C/EBPα.
Why the study?
Brown adipose tissue activation increases energy expenditure and offers a therapeutic strategy for obesity, but the role of lncRNA XIST in brown preadipocyte differentiation and metabolic regulation required evaluation.
Does XIST overexpression promote brown preadipocyte differentiation and prevent high-fat diet-induced obesity in mice?
Does XIST overexpression promote brown preadipocyte differentiation and prevent high-fat diet-induced obesity in mice?
p-value: p=<0.05
LncRNA XIST promotes brown preadipocyte differentiation and protects against high-fat diet-induced obesity in mice, suggesting a potential therapeutic target for obesity.
Supports XIST investigation in metabolic models; leaves open translation to human obesity therapy.
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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A 2022 study studied Obesity (n=35). XIST overexpression vs. Control plasmid (pCMV-CON) was evaluated on Body weight gain and brown preadipocyte differentiation (p=<0.05). Overexpression of lncRNA XIST promoted brown preadipocyte differentiation and prevented high-fat diet-induced weight gain in male mice by targeting C/EBPα.
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