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

Bal, Naresh C; Maurya, Santosh K; Sopariwala, Danesh H; Sahoo, Sanjaya K; Gupta, Subash C; Shaikh, Sana A; Pant, Meghna; Rowland, Leslie A; Goonasekera, Sanjeewa A; Molkentin, Jeffery D; Periasamy, Muthu

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.

SARCOLIPIN; BODY temperature regulation; ANIMAL models in research; SKELETAL muscle; ENDOPLASMIC reticulum; CALCIUM channels; ADENOSINE triphosphatase; HYPOTHERMIA

Nature Medicine, 2012, Vol 18, Issue 10, p1575

1078-8956

Academic Journal

10.1038/nm.2897