Role of endoplasmic reticulum stress induced eIF2alpha phosphorylation in skeletal muscle after exercise

在骨骼肌中，一些生理刺激，例如运动激活PERK-eIF 2 α磷酸化信号。Fv 2 E-PERK是一种人工合成的基因，由配体激活。我们产生了肌肉特异性Fv 2 E-PERK表达转基因（TG）小鼠。与野生型相比，饲喂高脂饮食的TG小鼠的肥胖减少。TG小鼠还改善了胰岛素敏感性和耗氧量。然而，骨骼肌中的代谢谱在野生型和TG小鼠之间似乎是相同的。令人惊讶的是，与能量消耗相关的基因表达在TG小鼠的棕色脂肪组织中高于野生型小鼠。一些实验表明PERK-eIF 2 α磷酸化单独调节骨骼肌中抗肥胖激素FGF 21的表达。TG小鼠的FGF 21血浆浓度也增加。这些结果表明，骨骼肌中eIF 2 α磷酸化诱导的FGF 21通过影响棕色脂肪组织增加能量消耗。

In skeletal muscle, some physiological stimulation, for example exercise activated PERK-eIF2alpha phosphorylation signal. Fv2E-PERK is artificial gene that is activated by ligand. We generated muscle-specific Fv2E-PERK expressing transgenic (TG) mice. Adiposity of TG mice fed high-fat diet was decreased compared from wild type. TG mice also improved insulin sensitivity and oxygen consumption. However, metabolic profile in skeletal muscle seemed to be same between wild type and TG mice. Surprisingly, gene expression related to energy expenditure was higher in brown adipose tissue of TG mice than in that of wild type mice. Some experiments showed that PERK-eIF2alpha phosphorylation single regulated anti obesity hormone FGF21 expression in skeletal muscle. Plasma concentration of FGF21 also increased in TG mice. These results suggest that FGF21 induced by eIF2alpha phosphorylation in skeletal muscle increases energy expenditure by affecting on brown adipose tissue.