Induction of adipocyte thermogenic program by Rho-associated coiled-coil containing kinase 2

Beige adipocytes develop within subcutaneous white adipose tissue (sWAT) and contribute to thermogenesis, vital for survival during cold exposure. Rho-associated coiled-coil containing kinase (ROCK) inhibitors have been found to promote white adipocyte differentiation. However, the adipocyte-specific role of ROCK2, the predominant ROCK isoform in adipocytes, in cold-induced thermogenesis is uncertain. Here, we show that ROCK2 in adipocytes is necessary for cold-induced adaptive beiging and thermogenesis. Cold exposure triggered a rapid ROCK activation in both sWAT and interscapular brown adipose tissue (iBAT) from wild-type mice. Mice lacking ROCK2 expression in adipocytes exhibited less cold-induced beige adipocyte development in sWAT and reduced thermogenesis in iBAT. In sWAT, cold-induced upregulation and nuclear translocation of forkhead box protein O1 (FOXO1) were critical for the ROCK2-mediated expression of thermogenic gene uncoupling protein 1 (Ucp1). Our findings indicate that ROCK2 promotes cold-induced beige adipocyte development and thermogenesis, suggesting that ROCK2 is a critical mediator of energy homeostasis.