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

摘要: The role of skeletal muscle in nonshivering thermogenesis (NST) is not well understood. Here we show that sarcolipin (Sln), a newly identified regulator the sarco/endoplasmic reticulum Ca(2+)-ATPase (Serca) pump, necessary for muscle-based thermogenesis. When challenged to acute cold (4 °C), Sln(-/-) mice were able maintain their core body temperature (37 °C) and developed hypothermia. Surgical ablation brown adipose tissue functional knockdown Ucp1 allowed us highlight NST. Overexpression Sln Sln-null background fully restored thermogenesis, suggesting basis Serca-mediated heat production. We ryanodine receptor 1 (Ryr1)-mediated Ca(2+) leak an important mechanism Serca-activated generation. present data suggest can continue interact with Serca presence Ca(2+), which promote uncoupling pump cause futile cycling. further loss predisposes diet-induced obesity, suggests Sln-mediated NST recruited during metabolic overload. These collectively SLN mediator whole-body energy metabolism.