bims-exemet Biomed News
on Exercise metabolism
Issue of 2021‒05‒30
eight papers selected by
Javier Botella Ruiz
Victoria University


  1. Cell Rep. 2021 May 25. pii: S2211-1247(21)00525-8. [Epub ahead of print]35(8): 109180
      Mitochondrial respiratory complex subunits assemble in supercomplexes. Studies of supercomplexes have typically relied upon antibody-based quantification, often limited to a single subunit per respiratory complex. To provide a deeper insight into mitochondrial and supercomplex plasticity, we combine native electrophoresis and mass spectrometry to determine the supercomplexome of skeletal muscle from sedentary and exercise-trained mice. We quantify 422 mitochondrial proteins within 10 supercomplex bands in which we show the debated presence of complexes II and V. Exercise-induced mitochondrial biogenesis results in non-stoichiometric changes in subunits and incorporation into supercomplexes. We uncover the dynamics of supercomplex-related assembly proteins and mtDNA-encoded subunits after exercise. Furthermore, exercise affects the complexing of Lactb, an obesity-associated mitochondrial protein, and ubiquinone biosynthesis proteins. Knockdown of ubiquinone biosynthesis proteins leads to alterations in mitochondrial respiration. Our approach can be applied to broad biological systems. In this instance, comprehensively analyzing respiratory supercomplexes illuminates previously undetectable complexity in mitochondrial plasticity.
    Keywords:  complexome; exercise; mitochondrial respiratory complexes; mitochondrial supercomplexes; oxidative phosphorylation; protein complexes
    DOI:  https://doi.org/10.1016/j.celrep.2021.109180
  2. J Physiol. 2021 May 25.
      KEY POINTS: A hallmark trait of aging skeletal muscle health is a reduction in size and function, which is most pronounced in the fast muscle fibers. We studied older men (74±4y) with a history of lifelong (>50y) endurance exercise to examine potential benefits for slow and fast muscle fiber size and contractile function. Lifelong endurance exercisers had slow muscle fibers that were larger, stronger, faster, and more powerful than young exercisers (25±1y) and age-matched non-exercisers (75±2y). Limited benefits with lifelong endurance exercise were noted in the fast muscle fibers. These findings suggest that additional exercise modalities (e.g., resistance exercise) or other therapeutic interventions are needed to target fast muscle fibers with age.ABSTRACT: We investigated single muscle fiber size and contractile function among three groups of men: lifelong exercisers (LLE; n = 21, 74±4y), old healthy non-exercisers (OH; n = 10, 75±2y), and young exercisers (YE; n = 10, 25±1y). On average, LLE exercised ∼5d/wk for ∼7h/wk over the past 53±6y. LLE were subdivided based on lifelong exercise intensity into performance (LLE-P, n = 14) and fitness (LLE-F, n = 7). Muscle biopsies (vastus lateralis) were examined for myosin heavy chain (MHC) slow (MHC I) and fast (MHC IIa) fiber size and function (strength, speed, power). LLE MHC I size (7624±2765 μm2 ) was 25-40% larger (P<0.001) than YE (6106±1710 μm2 ) and OH (5476±2467 μm2 ). LLE MHC I fibers were ∼20% stronger, ∼10% faster and ∼30% more powerful than YE and OH (P<0.05). In contrast, LLE MHC IIa size (6466±2659 μm2 ) was similar to OH (6237±2525 μm2 ; P = 0.854), with both groups ∼20% smaller (P<0.001) than YE (7860±1930 μm2 ). MHC IIa contractile function was variable across groups, with a hierarchical pattern (OH>LLE>YE; P<0.05) in normalized power among OH (16.7±6.4 W•L-1 ), LLE (13.9±4.5 W•L-1 ), and YE (12.4±3.5 W•L-1 ). The LLE-P and LLE-F had similar single fiber profiles with MHC I power driven by speed (LLE-P) or force (LLE-F), suggesting exercise intensity impacted slow muscle fiber mechanics. These data suggest that lifelong endurance exercise benefited slow muscle fiber size and function. Comparable fast fiber characteristics between LLE and OH, regardless of training intensity, suggest other exercise modes (e.g., resistance training) or myotherapeutics may be necessary to preserve fast muscle fiber size and performance with age. This article is protected by copyright. All rights reserved.
    Keywords:  aging; contractile function; masters athletes; myocellular; physical activity
    DOI:  https://doi.org/10.1113/JP281666
  3. Sci Rep. 2021 May 27. 11(1): 11261
      Thoroughbreds have high maximal oxygen consumption and show hypoxemia and hypercapnia during intense exercise, suggesting that the peripheral environment in skeletal muscle may be severe. Changes in metabolites following extreme alterations in the muscle environment in horses after exercise may provide useful evidence. We compared the muscle metabolites before and after supramaximal exercise to fatigue in horses. Six well-trained horses ran until exhaustion in incremental exercise tests. Biopsy samples were obtained from the gluteus medius muscle before and immediately after exercise for capillary electrophoresis-mass spectrometry analysis. In the incremental exercise test, the total running time and speed of the last step were 10.4 ± 1.3 (mean ± standard deviation) min and 12.7 ± 0.5 m/s, respectively. Of 73 metabolites, 18 and 11 were significantly increased and decreased after exercise, respectively. The heat map of the hierarchical cluster analysis of muscle metabolites showed that changes in metabolites were clearly distinguishable before and after exercise. Strenuous exercise increased many metabolites in the glycolytic pathway and the tricarboxylic acid cycle in skeletal muscle. Targeted metabolomic analysis of skeletal muscle may clarify the intramuscular environment caused by exercise and explain the response of working muscles to strenuous exercise that induces hypoxemia and hypercapnia in Thoroughbred horses.
    DOI:  https://doi.org/10.1038/s41598-021-90834-y
  4. FASEB J. 2021 Jun;35(6): e21644
      How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrβ3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.
    Keywords:  adipose tissue; extracellular vesicles; lipolysis; microRNAs; skeletal muscle
    DOI:  https://doi.org/10.1096/fj.202100242R
  5. Life Sci. 2021 May 24. pii: S0024-3205(21)00625-1. [Epub ahead of print] 119639
      AIMS: Strength training (ST) improves insulin resistance and glucose tolerance by yet unknown mechanisms. The aims of this study were to investigate the effects of ST on mitochondrial adaptation in skeletal muscle and adipose tissue, on heat shock protein 72 (Hsp72) in skeletal muscle, and on visceral adipocyte size in mice with high-fat diet (HFD)-induced insulin resistance.MATERIALS AND METHODS: Male Balb/c mice were divided into sedentary control-chow (C-chow), strength trained-chow (ST-chow), sedentary control-HFD (C-HFD) and strength trained-HFD (ST-HFD). Diet was provided for 12 weeks, while ladder climbing ST was performed for the final six weeks of the study at a frequency of three days per week.
    KEY FINDINGS: Strength training led to increased strength, muscular endurance, and skeletal muscle hypertrophy. Compared to the C-HFD group, mice in the ST-HFD group decreased their whole-body insulin resistance, improved their glucose tolerance, and had higher activation of the insulin pathway in skeletal muscle. ST increased citrate synthase (CS) activity in skeletal muscle, but this increase was blunted in ST-HFD. Conversely, HFD reduced adipose tissue CS activity regardless of training status. Hsp72 content was reduced in C-HFD, but returned to control levels in ST-HFD. Finally, reduced epididymal adipocyte size was observed in ST-HFD.
    SIGNIFICANCE: These results suggest that the improvement in insulin resistance induced by ST is related to mitochondrial adaptation in skeletal muscle, but not in adipose tissue. Moreover, this improvement might be related to increased skeletal muscle Hsp72 and reduced epididymal adipocyte size.
    Keywords:  Glucose metabolism; Glucose tolerance; Heat shock protein 72; Mitochondria; Obesity; Resistance training
    DOI:  https://doi.org/10.1016/j.lfs.2021.119639
  6. Physiol Rep. 2021 May;9(10): e14850
      Exercise training improves peripheral insulin sensitivity and leads to molecular adaptations in the skeletal muscle. We investigated changes in the expression of key muscle proteins in the glucose metabolic pathway following active commuting by bike or leisure-time exercise at two different intensities. In addition, potential associations between insulin sensitivity and muscle protein expression were examined. This per-protocol analysis included 72 out of 130 physically inactive, healthy women and men (20-45 years) with overweight/obesity (BMI: 25-35 kg/m2 ) who completed 6 months of no intervention (CON, n = 12), active commuting by bike (BIKE, n = 14), or leisure-time exercise of moderate (MOD, n = 28) or vigorous (VIG, n = 18) intensity. Exercise was prescribed 5 days/week with a weekly exercise energy expenditure of 1,600 kcal for women and 2,100 kcal for men. Insulin sensitivity was determined by a hyperinsulinemic euglycemic clamp and skeletal muscle biopsies were obtained from m. vastus lateralis and analyzed for protein expression at baseline and after 3 and 6 months of intervention. We found an increased expression of pyruvate dehydrogenase (PDH) in the exercise groups compared with the control group following 6 months of training. No differential effects were observed on the protein expression following moderate versus vigorous intensity exercise. In addition, we found a positive association between insulin sensitivity and the expression of glucose transporter type 4 as well as PDH. The positive association and the increase in expression of PDH after exercise training points toward a role for PDH in the training-induced enhancement of insulin sensitivity.
    Keywords:  PDH; exercise intensity; exercise training; insulin sensitivity
    DOI:  https://doi.org/10.14814/phy2.14850
  7. Sci Rep. 2021 May 24. 11(1): 10785
      This study examined whether intensity of endurance stimulus within a concurrent training paradigm influenced the phosphorylation of signaling proteins associated with the mTOR and AMPK networks. Eight male cyclists completed (1) resistance exercise (RES), 6 × 8 squats at 80% 1-RM; (2) resistance exercise and moderate intensity cycling of 40 min at 65% V̇O2peak, (RES + MIC); (3) resistance exercise and high intensity interval cycling of 40 min with 6 alternating 3 min intervals of 85 and 45% V̇O2peak (RES + HIIC), in a cross-over design. Muscle biopsies were collected at rest and 3 h post-RES. There was a main effect of condition for mTORS2448 (p = 0.043), with a greater response in the RES + MIC relative to RES condition (p = 0.033). There was a main effect of condition for AMPKα2T172 (p = 0.041), with a greater response in RES + MIC, relative to both RES + HIIC (p = 0.026) and RES (p = 0.046). There were no other condition effects for the remaining protein kinases assessed (p > 0.05). These data do not support a molecular interference effect in cyclists under controlled conditions. There was no intensity-dependent regulation of AMPK, nor differential activation of anabolism with the manipulation of endurance exercise intensity.
    DOI:  https://doi.org/10.1038/s41598-021-90274-8