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

运动对人体肌肉纤维类型特异性的 AMPK 及其下游靶点的调节

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

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.

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