The biophysical environment of membrane phospholipids affects structure, function, and stability of membrane-bound proteins.1,2 Obesity can disrupt membrane lipids, and in particular, alter the activity of sarco/endoplasmic reticulum (ER/SR) Ca2+-ATPase (SERCA) to affect cellular metabolism.3-5 Recent evidence suggests that transport efficiency (Ca2+ uptake / ATP hydrolysis) of skeletal muscle SERCA can be uncoupled to increase energy expenditure and protect mice from diet-induced obesity.6,7 In isolated SR vesicles, membrane phospholipid composition is known to modulate SERCA efficiency.8-11 Here we show that skeletal muscle SR phospholipids can be altered to decrease SERCA efficiency and increase whole-body metabolic rate. The absence of skeletal muscle phosphatidylethanolamine (PE) methyltransferase (PEMT) promotes an increase in skeletal muscle and whole-body metabolic rate to protect mice from diet-induced obesity. The elevation in metabolic rate is caused by a decrease in SERCA Ca2+-transport efficiency, whereas mitochondrial uncoupling is unaffected. Our findings support the hypothesis that skeletal muscle energy efficiency can be reduced to promote protection from obesity.

中文翻译：

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磷脂甲基化通过Ca2 +转运效率调节肌肉代谢率。

骨骼肌磷脂酰乙醇胺（PE）甲基转移酶（PEMT）的缺乏促进骨骼肌和全身代谢率的增加，从而保护小鼠免于饮食引起的肥胖。代谢率的升高是由SERCA Ca2 +转运效率的降低引起的，而线粒体的解偶联不受影响。我们的发现支持这样的假设，即可以降低骨骼肌的能量效率以促进对肥胖的保护。