AMPK——运动调控骨骼肌糖脂代谢的重要激酶

AMPK is an important kinase regulating exercise-induced glucose and fat metabolism in skeletal muscle

AMPK(5′AMP-activated protein kinase)是AMP激活的,由催化亚基α(α1/α2)、调节亚基β(β1/β2)和γ(γ1/γ2/γ3)构成的异源三聚体蛋白激酶。营养物质缺乏(无糖或低氧)、二甲双胍、AMPK激活剂AICAR和运动皆能激活骨骼肌AMPK,而AMPK主要促进骨骼肌分解代谢,抑制其合成代谢。其中,运动主要通过上调骨骼肌[AMP]/[ATP]或[ADP]/[ATP]比率促进AMPKαThr172位点磷酸化,从而激活骨骼肌AMPK介导的糖脂代谢信号通路,包括AMPK/TBC1D1/TBC1D4信号通路调控的GLUT4转位以促进葡萄糖摄取,以及AMPK/ACC(乙酰辅酶A羧化酶)信号通路结合线粒体蛋白转移酶CPT1/2和脂肪酸转运蛋白FAT/CD36、FABPpm和FATP1/4共同促进的骨骼肌脂肪酸氧化。为突出AMPK调控运动中骨骼肌糖脂代谢的重要性,本文分别阐述了运动对骨骼肌AMPK的调控作用,运动在骨骼肌AMPK介导糖、脂代谢中的调控作用。深度理解运动过程中AMPK调控骨骼肌糖脂代谢的细胞分子机制有助于将AMPK开发成治疗代谢类疾病的潜在有效靶向因子。

AMPK(5′AMP-activated protein kinase)is a heterotrimeric complex composed of catalyticα(α1/α2)subunit,regulatoryβ(β1/β2)andγ(γ1/γ2/γ3)subunits.Nutrient starvation(no glucose and/or hypoxia),metformin and AICAR(5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside)and exercise can activate AMPK,which promotes catabolism and inhibits anabolism in skeletal muscle.Exercise-induced elevation of[AMP]/[ATP]or[ADP]/[ATP]increases the phosphorylation of AMPKαThr172,thus regulating glucose uptake through AMPK/TBC1D1/TBC1D4 signaling pathway(promoting GLUT4 translocation to plasma membrane)and fatty acid oxidation through AMPK/ACC signaling pathway(in combination with mitochondrial proteins CPT1/2,fatty acid transporter proteins FAT/CD36,FABPpm and FATP1/4).To point out the significance of AMPK in the regulation of glucose and fat metabolism in exercised skeletal muscle,this review elucidates the regulation of exercise on AMPK in skeletal muscle,and the role of exercise in AMPK-induced glucose and fat metabolism.Therefore,understanding the molecular mechanisms of AMPK regulating glucose and fat metabolism in exercised skeletal muscle would accelerate AMPK as a potential and effective target molecule for treating metabolic diseases.