期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 290, 期 19, 页码 12282-12289出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M115.637603
关键词
adipose tissue; calcium ATPase; muscle physiology; sarcoplasmic reticulum (SR); skeletal muscle; skeletal muscle metabolism; uncoupling protein; sarcolipin; thermogenesis
资金
- National Institutes of Health [R01-HL088555, R01-DK098240-01]
Background: The mechanisms underlying UCP1-independent thermogenesis are not well understood. Results: Loss of both SLN and UCP1 results in compromised thermogenic ability and severe sensitivity to acute cold. Conclusion: Sarcolipin-mediated thermogenesis is required for optimal thermogenesis and is up-regulated in the absence of UCP1. Significance: Sarcolipin is a crucial contributor to thermogenesis and energy expenditure. 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. 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据