Research press release


Nature Medicine

Muscle as a key source of non-shivering thermogenesis



Muthu Periasamyたちは、筋肉も非ふるえ熱産生の起こる重要な部位の1つであることを明らかにし、このBAT中心説に疑問を呈した。筋肉のカルシウムポンプの負の調節因子であるサルコリピンが、細胞内カルシウム濃度が高いときにもカルシウムポンプと結合することに気付いたのである。この継続的調節がポンプの無駄な回転を引き起こし、ATPが使われて筋肉の非ふるえ型の熱生産につながる。サルコリピンをもたないマウスは、BATを外科的に除去すると、長く低温に曝されたときに中核体温を適切に維持できず、最終的には低体温症によって死んでしまう。これに対し、BATは除去したが正常レベルのサルコリピンをもつ野生型マウスでは中核体温は維持され、死ぬことはない。


Muscle is a key organ involved in long-term adaptation to the cold reports a study published this week in Nature Medicine. These findings could shed further light on how humans expend energy to heat up and therefore be of interest to other types of research, such as studies targeting obesity.

Mammals use their muscles to shiver to generate heat when exposed to the cold, but this response is a short-term adaptation. For long-term effects the body seems to rely on the brown adipose tissue (BAT) to generate heat in a non-shivering fashion.

Muthu Periasamy and colleagues challenge this BAT-centric view by showing that muscle is also a key site of non-shivering thermogenesis in mice. The authors found that sarcolipin-a negative regulator of a calcium pump in the muscle-interacts with this pump, even when levels of intracellular calcium are high. This continued regulation causes futile cycling of the pump resulting in ATP use and heat generation by the muscle in a non-shivering manner. Mice lacking sarcolipin could not properly maintain their core body temperature when challenged with a prolonged exposure to the cold and eventually died of hypothermia when the BAT was surgically removed. In contrast, wild-type mice lacking BAT, but having normal levels of sarcolipin, maintained their core body temperature and survived.

Periasamy and colleagues believe that although the study was performed solely in mice and the BAT function was not genetically inhibited, the findings suggest that the muscle is as important as the BAT in generating non-shivering thermogenesis. As the BAT has been recently proposed as a way to increase whole-body energy expenditure to combat obesity, this study indicates that the muscle and sarcolipin may be also targeted in obesity.

doi: 10.1038/nm.2897


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