Uncoupling Protein 1 and Sarcolipin Are Required to Maintain Optimal Thermogenesis and Loss of Both Systems Compromises Survival of Mice Under Cold Stress [Bioenergetics]

March 30th, 2015 by Rowland, L. A., Bal, N. C., Kozak, L. P., Periasamy, M.

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 BAT function is lacking. We recently showed that Sarcolipin, an uncoupler of the 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 if they are both necessary for thermogenesis. Towards this goal, we generated a UCP1; SLN double knockout (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 upregulation 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 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 loss of both systems compromises survival of mice under cold stress.
  • Posted in Journal of Biological Chemistry, Publications
  • Comments Off on Uncoupling Protein 1 and Sarcolipin Are Required to Maintain Optimal Thermogenesis and Loss of Both Systems Compromises Survival of Mice Under Cold Stress [Bioenergetics]