Cross talk between Skeletal muscle and Brown adipose tissue during cold and diet induced thermogeneis

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 Ca2+ 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. Interestingly loss of either SLN or UCP1 alone was sufficient to cause high fat diet‐induced obesity. No compensatory upregulation of UCP1 in SLN−/− mice or vice versa was found. However loss of both mechanisms failed to exacerbate the obesity phenotype. These studies imply that brown adipose tissue and skeletal muscle are recruited differently during cold vs diet induced thermogenesis.Support or Funding InformationNIH R01‐HL‐088555 and R01‐DK098240‐01American Diabetes Association Basic Science Research Award (7‐13‐BS‐131) (to MP) and by the NIDDK‐NIH Award (K01‐DK102772) (to NCB).