Myocardin-Related Transcription Factor A Regulates Conversion of Progenitors to Beige Adipocytes

Adipose tissue is an essential regulator of metabolic homeostasis. In contrast with white adipose tissue, which stores excess energy in the form of triglycerides, brown adipose tissue is thermogenic, dissipating energy as heat via the unique expression of the mitochondrial uncoupling protein UCP1. A subset of UCP1+ adipocytes develops within white adipose tissue in response to physiological stimuli; however, the developmental origin of these “brite” or “beige” adipocytes is unclear. Here, we report the identification of a BMP7-ROCK signaling axis regulating beige adipocyte formation via control of the G-actin-regulated transcriptional coactivator myocardin-related transcription factor A, MRTFA. White adipose tissue from MRTFA–/– mice contains more multilocular adipocytes and expresses enhanced levels of brown-selective proteins, including UCP1. MRTFA–/– mice also show improved metabolic profiles and protection from diet-induced obesity and insulin resistance. Our study hence unravels a central pathway driving the development of physiologically functional beige adipocytes. [Display omitted] •BMP7 induces brown adipogenesis in mesenchymal stem cells•BMP7 inhibits ROCK and promotes F- to G-actin conversion•Overexpression of MRTFA or SRF inhibits brown adipogenesis•Loss of MRTFA promotes browning and resistance to obesity A signaling axis driven by ROCK and the transcription factor MRTFA regulates the conversion of mesenchymal stem cells (MSCs) to brown-like (beige) adipocytes. Small molecule inhibitors or loss of MRTFA in mice leads to beige adipocyte formation, enhanced energy expenditure, and protection against diet-induced obesity.