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运动对人类肌肉纤维类型特异性的AMPK及其下游靶点的调节作用。

Human muscle fibre type-specific regulation of AMPK and downstream targets by exercise.

作者信息

Kristensen Dorte E, Albers Peter H, Prats Clara, Baba Otto, Birk Jesper B, Wojtaszewski Jørgen F P

机构信息

Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.

出版信息

J Physiol. 2015 Apr 15;593(8):2053-69. doi: 10.1113/jphysiol.2014.283267. Epub 2015 Feb 27.

Abstract

AMP-activated protein kinase (AMPK) is a regulator of energy homeostasis during exercise. Studies suggest muscle fibre type-specific AMPK expression. However, fibre type-specific regulation of AMPK and downstream targets during exercise has not been demonstrated. We hypothesized that AMPK subunits are expressed in a fibre type-dependent manner and that fibre type-specific activation of AMPK and downstream targets is dependent on exercise intensity. Pools of type I and II fibres were prepared from biopsies of vastus lateralis muscle from healthy men before and after two exercise trials: (1) continuous cycling (CON) for 30 min at 69 ± 1% peak rate of O2 consumption (V̇O2 peak ) or (2) interval cycling (INT) for 30 min with 6 × 1.5 min high-intensity bouts peaking at 95 ± 2% V̇O2 peak . In type I vs. II fibres a higher β1 AMPK (+215%) and lower γ3 AMPK expression (-71%) was found. α1 , α2 , β2 and γ1 AMPK expression was similar between fibre types. In type I vs. II fibres phosphoregulation after CON was similar (AMPK(Thr172) , ACC(Ser221) , TBC1D1(Ser231) and GS(2+2a) ) or lower (TBC1D4(Ser704) ). Following INT, phosphoregulation in type I vs. II fibres was lower (AMPK(Thr172) , TBC1D1(Ser231) , TBC1D4(Ser704) and ACC(Ser221) ) or higher (GS(2+2a) ). Exercise-induced glycogen degradation in type I vs. II fibres was similar (CON) or lower (INT). In conclusion, a differentiated response to exercise of metabolic signalling/effector proteins in human type I and II fibres was evident during interval exercise. This could be important for exercise type-specific adaptations, i.e. insulin sensitivity and mitochondrial density, and highlights the potential for new discoveries when investigating fibre type-specific signalling.

摘要

AMP激活的蛋白激酶(AMPK)是运动过程中能量稳态的调节因子。研究表明存在肌肉纤维类型特异性的AMPK表达。然而,运动过程中AMPK及其下游靶点的纤维类型特异性调节尚未得到证实。我们假设AMPK亚基以纤维类型依赖的方式表达,并且AMPK及其下游靶点的纤维类型特异性激活取决于运动强度。在两次运动试验前后,从健康男性股外侧肌活检样本中制备I型和II型纤维池:(1)以69±1%的峰值耗氧量(V̇O2峰值)持续骑行(CON)30分钟,或(2)间歇骑行(INT)30分钟,包括6次1.5分钟的高强度运动,峰值为95±2%V̇O2峰值。在I型纤维与II型纤维中,发现β1 AMPK表达更高(+215%),而γ3 AMPK表达更低(-71%)。α1、α2、β2和γ1 AMPK表达在纤维类型之间相似。在I型纤维与II型纤维中,CON后磷酸化调节相似(AMPK(Thr17​​2)、ACC(Ser221)、TBC1D1(Ser231)和GS(2 + 2a))或更低(TBC1D4(Ser704))。INT后,I型纤维与II型纤维中的磷酸化调节更低(AMPK(Thr17​​2)、TBC1D1(Ser231)、TBC1D4(Ser704)和ACC(Ser221))或更高(GS(2 + 2a))。I型纤维与II型纤维中运动诱导的糖原降解相似(CON)或更低(INT)。总之,在间歇运动期间,人类I型和II型纤维对代谢信号/效应蛋白运动的差异化反应很明显。这可能对运动类型特异性适应(即胰岛素敏感性和线粒体密度)很重要,并突出了在研究纤维类型特异性信号传导时新发现的潜力。

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