title: Uncoupling Protein 1 and Sarcolipin Are Required to Maintain Optimal Thermogenesis, and Loss of Both Systems Compromises Survival of Mice under Cold Stress.
abstract: The importance of brown adipose tissue as a site of nonshivering thermogenesis has been well documented. Emerging studies suggest that skeletal muscle is also an important site of thermogenesis especially when brown adipose tissue function is lacking. We recently showed that sarcolipin (SLN), an uncoupler of the sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) pump, could contribute to heat production in skeletal muscle. In this study, we sought to understand how loss of UCP1 or SLN is compensated during cold exposure and whether they are both necessary for thermogenesis. Toward this goal, we generated a UCP1;SLN double knock-out (DKO) mouse model and challenged the single and DKO mice to acute and long-term cold exposures. Results from this study show that there is up-regulation of SLN expression in UCP1-KO mice, and loss of SLN is compensated by increased expression of UCP1 and browning of white adipose tissue. We found that the DKO mice were viable when reared at thermoneutrality. When challenged to acute cold, the DKO were extremely cold-sensitive and became hypothermic. Paradoxically, the DKO mice were able to survive gradual cold challenge, but these mice lost significant weight and depleted their fat stores, despite having higher caloric intake. These studies suggest that UCP1 and SLN are required to maintain optimal thermogenesis and that loss of both systems compromises survival of mice under cold stress.
authors.affiliation: From the Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio 43210 and.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Rowland
authors.affiliation: From the Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio 43210 and.
authors.forename: Naresh C
authors.initials: NC
authors.lastname: Bal
authors.affiliation: the Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
authors.forename: Leslie P
authors.initials: LP
authors.lastname: Kozak
authors.affiliation: From the Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio 43210 and periasamy.1@osu.edu.
authors.forename: Muthu
authors.initials: M
authors.lastname: Periasamy
mesh_terms: D002001:Adipose Tissue, Brown / Q000502:physiology*; D000818:Animals; D001835:Body Weight; D002395:Catecholamines / Q000652:urine; D003080:Cold Temperature; D005260:Female; D007473:Ion Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D010101:Oxygen Consumption; D011510:Proteolipids / Q000502:physiology*; D013312:Stress, Physiological; D022722:Thermogenesis; D000071256:Uncoupling Protein 1; D015854:Up-Regulation
chemical_list: D002395:Catecholamines; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D011510:Proteolipids; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C077258:sarcolipin
keywords: adipose tissue; calcium ATPase; muscle physiology; sarcolipin; sarcoplasmic reticulum (SR); skeletal muscle; skeletal muscle metabolism; thermogenesis; uncoupling protein
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