AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training

2009 ◽  
Vol 107 (1) ◽  
pp. 283-289 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Benedict J. Canny ◽  
Damian E. Myers ◽  
Glenn K. McConell

AMP-activated protein kinase (AMPK) has been extensively studied in whole muscle biopsy samples of humans, yet the fiber type-specific expression and/or activation of AMPK is unknown. We examined basal and exercise AMPK-α Thr172 phosphorylation and AMPK subunit expression (α1, α2, and γ3) in type I, IIa, and IIx fibers of human skeletal muscle before and after 10 days of exercise training. Before training basal AMPK phosphorylation was greatest in type IIa fibers ( P < 0.05 vs. type I and IIx), while an acute bout of exercise increased AMPK phosphorylation in all fibers ( P < 0.05), with the greatest increase occurring in type IIx fibers. Exercise training significantly increased basal AMPK phosphorylation in all fibers, and the exercise-induced increases were uniformly suppressed compared with pretraining exercise. Expression of AMPK-α1 and -α2 was similar between fibers and was not altered by exercise training. However, AMPK-γ3 was differentially expressed in skeletal muscle fibers (type IIx > type IIa > type I), irrespective of training status. Thus skeletal muscle AMPK phosphorylation and AMPK expression are fiber type specific in humans in the basal state, as well as during exercise. Our findings reveal fiber type-specific differences that have been masked in previous studies examining mixed muscle samples.

2007 ◽  
Vol 103 (6) ◽  
pp. 2105-2111 ◽  
Author(s):  
A. R. Tupling ◽  
E. Bombardier ◽  
R. D. Stewart ◽  
C. Vigna ◽  
A. E. Aqui

To investigate the time course of fiber type-specific heat shock protein 70 (Hsp70) expression in human skeletal muscle after acute exercise, 10 untrained male volunteers performed single-legged isometric knee extensor exercise at 60% of their maximal voluntary contraction (MVC) with a 50% duty cycle (5-s contraction and 5-s relaxation) for 30 min. Muscle biopsies were collected from the vastus lateralis before (Pre) exercise in the rested control leg (C) and immediately after exercise (Post) in the exercised leg (E) only and on recovery days 1 (R1), 2 (R2), 3 (R3), and 6 (R6) from both legs. As demonstrated by Western blot analysis, whole muscle Hsp70 content was unchanged ( P > 0.05) immediately after exercise (Pre vs. Post), was increased ( P < 0.05) by ∼43% at R1, and remained elevated throughout the entire recovery period in E only. Hsp70 expression was also assessed in individual muscle fiber types I, IIA, and IIAX/IIX by immunohistochemistry. There were no fiber type differences ( P > 0.05) in basal Hsp70 expression. Immediately after exercise, Hsp70 expression was increased ( P < 0.05) in type I fibers by ∼87% but was unchanged ( P > 0.05) in type II fibers (Pre vs. Post). At R1 and throughout recovery, Hsp70 content in E was increased above basal levels ( P < 0.05) in all fiber types, but Hsp70 expression was always highest ( P < 0.05) in type I fibers. Hsp70 content in C was not different from Pre at any time throughout recovery. Glycogen depletion was observed at Post in all type II, but not type I, fibers, suggesting that the fiber type differences in exercise-induced Hsp70 expression were not related to glycogen availability. These results demonstrate that the time course of exercise-induced Hsp70 expression in human skeletal muscle is fiber type specific.


Diabetes ◽  
2000 ◽  
Vol 49 (7) ◽  
pp. 1092-1095 ◽  
Author(s):  
J R Daugaard ◽  
J N Nielsen ◽  
S Kristiansen ◽  
J L Andersen ◽  
M Hargreaves ◽  
...  

2020 ◽  
Vol 134 ◽  
pp. 110880 ◽  
Author(s):  
V.L. Wyckelsma ◽  
W. Lindkvist ◽  
T. Venckunas ◽  
M. Brazaitis ◽  
S. Kamandulis ◽  
...  

Author(s):  
Nanna Skytt Pilmark ◽  
Laura Oberholzer ◽  
Jens Frey Halling ◽  
Jonas M. Kristensen ◽  
Christina Pedersen Bønding ◽  
...  

Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise +/- metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g. the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty bullets • Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle • Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle • Metformin does not affect exercise-induced AMPK activation in human skeletal muscle


2012 ◽  
Vol 22 (4) ◽  
pp. 292-303 ◽  
Author(s):  
Ildus I. Ahmetov ◽  
Olga L. Vinogradova ◽  
Alun G. Williams

The ability to perform aerobic or anaerobic exercise varies widely among individuals, partially depending on their muscle-fiber composition. Variability in the proportion of skeletal-muscle fiber types may also explain marked differences in aspects of certain chronic disease states including obesity, insulin resistance, and hypertension. In untrained individuals, the proportion of slow-twitch (Type I) fibers in the vastus lateralis muscle is typically around 50% (range 5–90%), and it is unusual for them to undergo conversion to fast-twitch fibers. It has been suggested that the genetic component for the observed variability in the proportion of Type I fibers in human muscles is on the order of 40–50%, indicating that muscle fiber-type composition is determined by both genotype and environment. This article briefly reviews current progress in the understanding of genetic determinism of fiber-type proportion in human skeletal muscle. Several polymorphisms of genes involved in the calcineurin–NFAT pathway, mitochondrial biogenesis, glucose and lipid metabolism, cytoskeletal function, hypoxia and angiogenesis, and circulatory homeostasis have been associated with fiber-type composition. As muscle is a major contributor to metabolism and physical strength and can readily adapt, it is not surprising that many of these gene variants have been associated with physical performance and athlete status, as well as metabolic and cardiovascular diseases. Genetic variants associated with fiber-type proportions have important implications for our understanding of muscle function in both health and disease.


2018 ◽  
Vol 125 (2) ◽  
pp. 470-478 ◽  
Author(s):  
Martin Thomassen ◽  
Morten Hostrup ◽  
Robyn M. Murphy ◽  
Brett A. Cromer ◽  
Casper Skovgaard ◽  
...  

Cl− channel protein 1 (ClC-1) may be important for excitability and contractility in skeletal muscle, but ClC-1 abundance has not been examined in human muscle. The aim of the present study was to examine ClC-1 abundance in human skeletal muscle, including fiber type specific differences and the effect of exercise training. A commercially available antibody was tested with positive and negative control tissue, and it recognized specifically ClC-1 in the range from 100 to 150 kDa. Abundance of ClC-1 was 38% higher ( P < 0.01) in fast twitch Type IIa muscle fibers than in slow twitch Type I. Muscle ClC-1 abundance did not change with 4 wk of training consisting of 30 min cycling at 85% of maximal heart rate (HRmax) and 3 × 30-s all out sprints or during a 7-wk training period with 10–12 × 30 s uphill cycling and 4–5 × ~4 min cycling at 90%–95% of HRmax. ClC-1 abundance correlated negatively ( P < 0.01) with maximal oxygen consumption ( r = –0.552) and incremental exercise performance ( r = –0.546). In addition, trained cyclists had lower ( P < 0.01) ClC-1 abundance than lesser trained individuals. The present observations indicate that a low abundance of muscle ClC-1 may be beneficial for exercise performance, but the role of abundance and regulation of ClC-1 in skeletal muscle of humans with respect to exercise performance and trainability need to be elucidated. NEW & NOTEWORTHY Abundance of the Cl− channel protein 1 (ClC-1) chloride channel may be important for excitability and contractility in human skeletal muscle and may therefore have implications for fatigue development. In this study, we confirmed ClC-1 specificity for a commercially available antibody, and this study is first to our knowledge to determine ClC-1 protein abundance in human muscle by Western blotting. We observed that abundance of ClC-1 was higher in fast compared with slow twitch fibers and lower in trained individuals than in recreationally active.


2004 ◽  
Vol 287 (2) ◽  
pp. R397-R402 ◽  
Author(s):  
Lotte Jensen ◽  
Henriette Pilegaard ◽  
P. Darrell Neufer ◽  
Ylva Hellsten

The present study investigated the effect of an acute exercise bout on the mRNA response of vascular endothelial growth factor (VEGF) splice variants in untrained and trained human skeletal muscle. Seven habitually active young men performed one-legged knee-extensor exercise training at an intensity corresponding to ∼70% of the maximal workload in an incremental test five times/week for 4 wk. Biopsies were obtained from the vastus lateralis muscle of the trained and untrained leg 40 h after the last training session. The subjects then performed 3 h of two-legged knee-extensor exercise, and biopsies were obtained from both legs after 0, 2, 6, and 24 h of recovery. Real-time PCR was used to examine the expression of VEGF mRNA containing exon 1 and 2 (all VEGF isoforms), exon 6 or exon 7, and VEGF165mRNA. Acute exercise induced an increase ( P < 0.05) in total VEGF mRNA levels as well as VEGF165and VEGF splice variants containing exon 7 at 0, 2, and 6 h of recovery. The increase in VEGF mRNA was higher in the untrained than in the trained leg ( P < 0.05). The results suggest that in human skeletal muscle, acute exercise increases total VEGF mRNA, an increase that appears to be explained mainly by an increase in VEGF165mRNA. Furthermore, 4 wk of training attenuated the exercise-induced response in skeletal muscle VEGF165mRNA.


2013 ◽  
Vol 304 (12) ◽  
pp. E1379-E1390 ◽  
Author(s):  
Brynjulf Mortensen ◽  
Janne R. Hingst ◽  
Nicklas Frederiksen ◽  
Rikke W. W. Hansen ◽  
Caroline S. Christiansen ◽  
...  

Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling. We investigated 21 LBW and 21 normal birth weight (NBW) subjects during 1 h of acute exercise performed at the same relative workload before and after 12 wk of exercise training. Multiple skeletal muscle biopsies were obtained before and after exercise. Protein levels and phosphorylation status were determined by Western blotting. AMPK activities were measured using activity assays. Protein levels of AMPKα1 and -γ1 were significantly increased, whereas AMPKγ3 levels decreased with training independently of group. The LBW group had higher exercise-induced AMPK Thr172 phosphorylation before training and higher exercise-induced ACC2 Ser221 phosphorylation both before and after training compared with NBW. Despite exercise being performed at the same relative intensity (65% of V̇o2peak), the acute exercise response on AMPK Thr172, ACC2 Ser221, AMPKα2β2γ1, and AMPKα2β2γ3 activities, GS activity, and adenine nucleotides as well as hexokinase II mRNA levels were all reduced after exercise training. Increased exercise-induced muscle AMPK activation and ACC2 Ser221 phosphorylation in LBW subjects may indicate a more sensitive AMPK system in this population. Long-term exercise training may reduce the need for AMPK to control energy turnover during exercise. Thus, the remaining γ3-associated AMPK activation by acute exercise after exercise training might be sufficient to maintain cellular energy balance.


2021 ◽  
Vol 130 (4) ◽  
pp. 1001-1014
Author(s):  
Lauren E. Skelly ◽  
Jenna B. Gillen ◽  
Barnaby P. Frankish ◽  
Martin J. MacInnis ◽  
F. Elizabeth Godkin ◽  
...  

We examined mixed-muscle and fiber type-specific responses to a single session and to 12 wk of moderate-intensity continuous training (MICT) and sprint interval training (SIT) in humans. Both interventions elicited generally similar responses, although the training-induced increases in type I fiber-specific markers of mitochondrial content were greater in MICT than in SIT. These findings advance our understanding of the potential role of fiber type-specific changes in determining the human skeletal muscle response to intermittent and continuous exercise.


Author(s):  
Oscar Horwath ◽  
Helena Envall ◽  
Julia Röja ◽  
Eric Bengt Emanuelsson ◽  
Gema Sanz ◽  
...  

Human skeletal muscle characteristics such as fiber type composition, fiber size and myonuclear content are widely studied in clinical and sports related contexts. Being aware of the methodological and biological variability of the characteristics is a critical aspect in study design and outcome interpretation, but comprehensive data on the variability of morphological features in human skeletal muscle is currently limited. Accordingly, in the present study, m. vastus lateralis biopsies (10 per subject) from young and healthy individuals, collected in a systematic manner, were analyzed for various characteristics using immunohistochemistry (n=7) and SDS-PAGE (n=25). None of the analyzed parameters; fiber type % (FT%), type I and II CSA (fCSA), percentage fiber type area (fCSA%), myosin heavy chain composition (MyHC%), type IIX content, myonuclear content or myonuclear domain varied in a systematic manner longitudinally along the muscle or between the two legs. The average within subject coefficient of variation for FT%, fCSA, fCSA%, and MyHC% ranged between 13-18%, but was only 5% for fiber specific myonuclear content, which reduced the variability for myonuclear domain size to 11-12%. Pure type IIX fibers and type IIX MyHC were randomly distributed and present in <24% of the analyzed samples, with the average content being 0.1 and 1.1%, respectively. In conclusion, leg or longitudinal orientation does not seem to be an important aspect to consider when investigating human vastus lateralis characteristics. However, single muscle biopsies should preferably not be used when studying fiber type and fiber size related aspects given the notable sample to sample variability.


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