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

在骨骼肌中，一些生理刺激，如运动，激活了PERK-eIF2alpha磷酸化信号。Fv2E-PERK是一种由配体激活的人工基因。我们产生了表达肌肉特异性Fv2E-PERK的转基因（TG）小鼠。与野生型相比，高脂饲料能降低TG小鼠的肥胖程度。甘油三酯小鼠也改善了胰岛素敏感性和耗氧量。然而，骨骼肌代谢谱在野生型和TG小鼠之间似乎是相同的。令人惊讶的是，TG小鼠棕色脂肪组织中与能量消耗相关的基因表达高于野生型小鼠。有实验表明，PERK-eIF2alpha磷酸化单调控骨骼肌中抗肥胖激素FGF21的表达。TG小鼠血浆FGF21浓度升高。这些结果表明，骨骼肌中eIF2alpha磷酸化诱导的FGF21通过影响棕色脂肪组织来增加能量消耗。

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.