Circular RNA SAMD4A controls adipogenesis in obesity through the miR-138-5p/EZH2 axis

A growing body of evidence has suggested that circular RNAs (circRNAs) are crucial for the regulation of gene expression and their dysregulation is implicated in several diseases. However, the function of circRNAs in obesity remains largely unexplored. Methods: Global changes in the circRNA expression patterns were detected in adipose tissues derived from obese and lean individuals. In particular, circSAMD4A was identified as significantly differentially upregulated and was functionally analyzed, both in vitro and in vivo, using various approaches. Results: CircSAMD4A overexpression was correlated with a poor prognosis in obese patients. By contrast, circSAMD4A knockdown inhibited differentiation in isolated preadipocytes. In high-fat diet (HFD) -induced obese mice, circSAMD4A knockdown reversed the associated weight gain, reduced food intake, lower body fat, and increased energy expenditure. These mice also exhibited increased insulin sensitivity and glucose tolerance. Furthermore, in vitro experiments indicated that circSAMD4A affected differentiation by binding to miR-138-5p and regulating EZH2 expression. Conclusions: CircSAMD4A regulated preadipocyte differentiation by acting as a miR-138-5p sponge, and thus increasing EZH2 expression. These results suggested that circSAMD4A can serve as a potential target for obesity treatments and/or as a potential prognostic marker for obese patients following bariatric surgery.