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Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals
Open accessAbstract
The role of skeletal muscle in nonshivering thermogenesis (NST) is not well understood. Here we show that sarcolipin (Sln), a newly identified regulator of the sarco/endoplasmic reticulum Ca2+-ATPase (Serca) pump, is necessary for muscle-based thermogenesis. When challenged to acute cold (4 °C), Sln−/− mice were not able to maintain their core body temperature (37 °C) and developed hypothermia. Surgical ablation of brown adipose tissue and functional knockdown of Ucp1 allowed us to highlight the role of muscle in NST. Overexpression of Sln in the Sln-null background fully restored muscle-based thermogenesis, suggesting that Sln is the basis for Serca-mediated heat production. We show that ryanodine receptor 1 (Ryr1)-mediated Ca2+ leak is an important mechanism for Serca-activated heat generation. Here we present data to suggest that Sln can continue to interact with Serca in the presence of Ca2+, which can promote uncoupling of the Serca pump and cause futile cycling. We further show that loss of Sln predisposes mice to diet-induced obesity, which suggests that Sln-mediated NST is recruited during metabolic overload. These data collectively suggest that SLN is an important mediator of muscle thermogenesis and whole-body energy metabolism.
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“Binding of SLN to SERCA reduces the efficiency of Ca2+ transport, resulting in more ATP being used to transport the same amount of Ca2+, thus leading to increased energy expenditure and heat production (103).”
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Metadata
- Authors
- Bal, N. C., Maurya, S. K., Sopariwala, D. H., Sahoo, S. K., Gupta, S. C., Shaikh, S. A., Pant, M., Rowland, L. A., Bombardier, E., Goonasekera, S. A., Tupling, A. R., Molkentin, J. D., & Periasamy, M.
- Venue
- Nature Medicine
- Published
- 2012-09-09
- Volume
- 18
- Issue
- 10
- Pages
- 1575-1579
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2065656177
- Cited by
- 553
- References
- 2
- FWCI
- 22.64
- Type
- journal article
- Language
- en
- Open access
- green
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