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Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals.

Authors: Bal, Naresh C  Maurya, Santosh K  Sopariwala, Danesh H  Sahoo, Sanjaya K  Gupta, Subash C  Shaikh, Sana A  Pant, Meghna  Rowland, Leslie A  Bombardier, Eric  Goonasekera, Sanjeewa A  Tupling, A Russell  Molkentin, Jeffery D  Periasamy, Muthu 
Citation: Bal NC, etal., Nat Med. 2012 Oct;18(10):1575-9. doi: 10.1038/nm.2897. Epub 2012 Sep 9.
Pubmed: (View Article at PubMed) PMID:22961106
DOI: Full-text: DOI:10.1038/nm.2897

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 Ca(2+)-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 Ca(2+) 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 Ca(2+), 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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RGD ID: 13673770
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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