miR-21 blocks obesity in mice: a potential therapy for humans

microRNAs are promising drug targets in obesity and metabolic disorders. miR-21 expression is upregulated in obese white adipose tissue (WAT), ‎however, its physiological role in WAT has not been fully explored. We aimed to ‎dissect the underlying molecular mechanisms of miR-21 in treating obesity, diabetes, ‎and insulin resistance. We demonstrated, in human and mice, that elevated miR-21 ‎expression is associated with metabolically healthy obesity. miR-21 mimic affected ‎the expression of genes associated with adipogenesis, thermogenesis, and browning in ‎‎3T3-L1 adipocytes. In addition, it blocked high fat diet-induced weight gain in obese ‎mice, without modifying food intake or physical activity. This was associated with ‎metabolic enhancements, WAT browning and thermogenic programming, and brown ‎AT induction through VEGF-A, p53, and TGFβ1 signaling pathways. Our findings add ‎a novel role of miR-21 in the regulation of obesity and a potential therapy for both ‎obesity and T2D without altering caloric intake and physical activities.