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

Abstract

Keypointsr AMP-activated protein kinase (AMPK) is an important regulator of cellular energy status during exercise.r Most human studies investigating skeletal muscle protein signalling have been performed in whole muscle biopsy samples, yet recent studies suggest muscle fibre type-specific AMPK expression with potential fibre type-specific regulation of AMPK during exercise.r This study provides novel and comprehensive data on human muscle fibre type-specific expression levels of AMPK subunits and downstream targets of AMPK.r We show a differentiated response to exercise of key metabolic signalling proteins in human type I and type II muscle fibres during interval exercise, not evident during continuous exercise. These differences between exercise types were not present in whole muscle biopsy samples.r Our findings highlight the importance of performing fibre type-specific measurements and the increased activation of AMPK in interval vs. continuous exercise could be important for exercise type-specific adaptations, i.e. metabolism, insulin sensitivity and mitochondrial density in human skeletal muscle.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 O 2 consumption (V O 2 peak ) or (2) interval cycling (INT) for 30 min with 6 × 1.5 min high-intensity bouts peaking at 95 ± 2%V O 2 peak . In type I vs. II fibres a higher β 1 AMPK (+215%) and lower γ 3 AMPK expression (−71%) was found. 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

Promoter-specific regulation of PPARGC1A gene expression in human skeletal muscle

“…In our study, activation of AMPK after HE might be associated with high AMP/ATP ratio and/or low post-exercise muscle glycogen level (Richter & Ruderman 2009), both changes being a result either of higher intensity itself or recruitment of highthreshold fibres (Kristensen et al 2015). Expression via the canonical promoter may also be regulated by the kinases p38 MAPK Thr180/Tyr182 and CaMKII Thr286 , through activation of MEF2C (McGee & Hargreaves 2004) and CREB1-related protein, activating transcription factor 2 (ATF2) (Akimoto et al 2005, Wright et al 2007.…”

Preservation of skeletal muscle mitochondrial content in older adults: relationship between mitochondria, fibre type and high‐intensity exercise training

“…The specific upregulation of NDUFA9 in type II fibres may be related to the exercise employed which may recruit more type II fibres (Kristensen et al . ), at least in comparison to regular every day activities of the older adults.…”

Increased FXYD1 and PGC‐1α mRNA after blood flow‐restricted running is related to fibre type‐specific AMPK signalling and oxidative stress in human muscle

“…The remainder of each denatured fibre segment (7 μL) was grouped according to MHC expression to form samples of type I (MHCI) and type II (MHCIIa) fibres for each biopsy, in line with previous procedure . The number of fibre segments included in each group of muscle fibres per biopsy was (mean ± SD) n = 12 ± 6 (range: 5‐27) for type I, and n = 16 ± 5 (range 7‐33) for type IIa, fibres.…”