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• Bal 2016 J Biol Chem  + (Skeletal muscle has been suggested as a si … Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides Brown Adipose Tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle based NST. However, the muscle-based-NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum (SER) Ca²⁺-cycling and its regulation by sarcolipin (SLN) can be the basis for muscle-NST. Due to the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study we investigated if muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT; constitute ~70% of total BAT) and exposed the mice to prolonged cold (4 deg C) for 9 day. The iBAT-ablated mice were able to maintain optimal body temperature (~35-37 deg C) during the entire period of cold exposure. After 4 days in cold, both sham controls and iBAT-ablated mice stopped shivering, resumed routine physical activity indicating that they are cold adapted. The iBAT-ablated mice showed higher oxygen consumption, decreased body-weight and fat-mass suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both SR and mitochondria including alteration in the expression of key components of Ca²⁺-handling, and mitochondrial metabolism. These changes along with increased SLN expression provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST, when BAT activity is minimized.</br></br>Copyright © 2016, The American Society for Biochemistry and Molecular Biology.2016, The American Society for Biochemistry and Molecular Biology.)

• Bal 2016 J Biol Chem  +