Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.
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, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca(2+) cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35-37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and 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 the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca(2+) handling and mitochondrial metabolism. These changes, along with increased sarcolipin 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.
From the Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, the Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio 43210, the School of Biotechnology, KIIT University, Bhubaneswar, Odisha, India 751024, and nbal@sbpdiscovery.org naresh.bal@kiitbiotech.ac.in.
Naresh C
NC
Bal
From the Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, the Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio 43210.
Santosh K
SK
Maurya
From the Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, the Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio 43210.
Sushant
S
Singh
the Cardiovascular Research Institute, Departments of Molecular Physiology and Biophysics, Medicine, and Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Xander H T
XH
Wehrens
From the Sanford Burnham Prebys Medical Discovery Institute at Lake Nona, Orlando, Florida 32827, the Department of Physiology and Cell Biology, College of Medicine, Ohio State University, Columbus, Ohio 43210.
Muthu
M
Periasamy
D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D003080:Cold Temperature; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology*; D022722:Thermogenesis / Q000502:physiology*
brown adipose tissue; calcium transport; cold adaptation; core body temperature; mitochondria; mitochondrial dynamics; mitochondrial metabolism; sarcoplasmic reticulum (SR); skeletal muscle