Endocrine Abstracts

Obesity results from the excess accumulation of energy in white adipocytes (WAs), leading to metabolic disorders such as diabetes. In contrast, beige and brown adipocytes (BAs) generate heat through non-shivering thermogenesis. Since brown adipose tissue (BAT) dissipates energy and counteracts fat accumulation, stimulating BAT activation and white adipose tissue (WAT) browning may provide an effective approach to treat obesity. MicroRNAs (miRNAs), small non-coding RNAs that regulate gene expression, have emerged as key modulators of adipogenesis and metabolic function. Here we found that miR-10b-5p plays an essential role in adipogenesis in BAT and WAT. Small RNAseq analysis of primary mouse BAs and WAs identified miR-10b-5p to be upregulated in mature BAs. MiR-10b-5p depletion severely compromised differentiation into mature BAs as judged by lack of lipid droplet accumulation and decreased expression of adipogenic markers. RNA sequencing revealed a significant increase in genes related to G Protein signalling associated with elevated Tubby (Tub). Consistent with transcriptomic findings, Tub mRNA and protein levels increased with miR-10b-5p inhibition in BAs. Next, we investigated the effects of miR-10b-5p upregulation on WA differentiation. Elevated abundance of miR-10b-5p in WAs significantly enhanced white adipogenesis as judged by the increased production of lipid droplets and elevated expression of adipogenic markers. We also observed increased Ucp1 and Ppargc1a levels during white adipogenesis, indicating an increase in the expression of the thermogenic gene program. The miR-10b-5p mimic during WA differentiation instigated a substantial increase in maximal respiration, ATP production coupled respiration and proton leak, indicating a higher mitochondrial uncoupling, which could potentially contribute to thermogenesis. Upon activation of β-adrenergic signalling, a robust increase of Ucp1 and Ppargc1a was detected. Our research work demonstrates that miR-10b-5p modulates adipocyte differentiation and fat browning. These findings strengthen the therapeutic possibility of using miRNAs to control obesity and its associated diseases in humans.