Brown Adipose Tissue and Skeletal Muscle Coordinately Contribute to Thermogenesis in Mice

Abstract Endotherms increase the rate of metabolism in metabolic organs as one strategy to cope with a decline in temperature of the external environment. However, an additional major contributor to maintenance of body temperature in a cold environment is contraction-based thermogenesis in skeletal muscle. Here we show that impairment of hind limb muscle contraction by cast immobilization suppresses skeletal muscle thermogenesis and activates brown adipose tissue (BAT) thermogenesis as a compensatory mechanism. BAT utilizes free branched-chain amino acids (BCAAs) derived from skeletal muscle as an energy substrate for thermogenesis, and interleukin-6 released by skeletal muscle stimulates BCAA production in muscle for support of BAT thermogenesis. Our findings suggest that BAT and skeletal muscle cooperate to maintain body temperature in endotherms.