bims-misrem Biomed News
on Mitochondria and sarcoplasmic reticulum in muscle mass
Issue of 2021–11–21
six papers selected by
Rafael Antonio Casuso Pérez, University of Granada
  1. Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials.
  2. Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users.
  3. The role of mitochondrial reactive oxygen species in insulin resistance.
  4. Exercise does not improve insulin resistance and mitochondrial characteristics together.
  5. Skeletal Muscle Adaptations and Performance Outcomes Following a Step and Exponential Taper in Strength Athletes.
  6. Insulin, Muscle Glucose Uptake, and Hexokinase: Revisiting the Road Not Taken.
  1. Appl Physiol Nutr Metab. 2021 Nov 16.
    Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of two randomised, clinical trials.
    Nanna Skytt Pilmark, Laura Oberholzer, Jens Frey Halling, Jonas M Kristensen, Christina Pedersen Bønding, Ida Elkjær, Mark Lyngbæk, Grit Elster, Christoph Siebenmann, Niels Frederich Holm, Jesper Bratz Bratz Birk, Emil List Larsen, Anne-Kristine Meinild-Lundby, J F Wojtaszewski, Henriette Pilegaard, Henrik Poulsen, Bente Klarlund Pedersen, Katrine Bagge Hansen, Kristian Karstoft.
      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.
    DOI:  https://doi.org/10.1139/apnm-2021-0194
  2. J Am Coll Cardiol. 2021 Nov 23. pii: S0735-1097(21)06335-X. [Epub ahead of print]78(21): 2023-2037
    Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users.
    Neeltje A E Allard, Lando Janssen, Thorben Aussieker, Anouk A F Stoffels, Richard J Rodenburg, Willem J J Assendelft, Paul D Thompson, Tim Snijders, Maria T E Hopman, Silvie Timmers.
       BACKGROUND: The combination of statin therapy and physical activity reduces cardiovascular disease risk in patients with hyperlipidemia more than either treatment alone. However, mitochondrial dysfunction associated with statin treatment could attenuate training adaptations.
    OBJECTIVES: This study determined whether moderate intensity exercise training improved muscle and exercise performance, muscle mitochondrial function, and fiber capillarization in symptomatic and asymptomatic statin users.
    METHODS: Symptomatic (n = 16; age 64 ± 4 years) and asymptomatic statin users (n = 16; age 64 ± 4 years) and nonstatin using control subjects (n = 20; age 63 ± 5 years) completed a 12-week endurance and resistance exercise training program. Maximal exercise performance (peak oxygen consumption), muscle performance and muscle symptoms were determined before and after training. Muscle biopsies were collected to assess citrate synthase activity, adenosine triphosphate (ATP) production capacity, muscle fiber type distribution, fiber size, and capillarization.
    RESULTS: Type I muscle fibers were less prevalent in symptomatic statin users than control subjects at baseline (P = 0.06). Exercise training improved muscle strength (P < 0.001), resistance to fatigue (P = 0.01), and muscle fiber capillarization (P < 0.01), with no differences between groups. Exercise training improved citrate synthase activity in the total group (P < 0.01), with asymptomatic statin users showing less improvement than control subjects (P = 0.02). Peak oxygen consumption, ATP production capacity, fiber size, and muscle symptoms remained unchanged in all groups following training. Quality-of-life scores improved only in symptomatic statin users following exercise training (P < 0.01).
    CONCLUSIONS: A moderate intensity endurance and resistance exercise training program improves muscle performance, capillarization, and mitochondrial content in both asymptomatic and symptomatic statin users without exacerbating muscle complaints. Exercise training may even increase quality of life in symptomatic statin users. (The Effects of Cholesterol-Lowering Medication on Exercise Performance [STATEX]; NL5972/NTR6346).
    Keywords:  combined exercise training; exercise performance; mitochondrial dysfunction; muscle fiber type distribution; statin-associated muscle symptoms
    DOI:  https://doi.org/10.1016/j.jacc.2021.08.075
  3. Free Radic Biol Med. 2021 Nov 11. pii: S0891-5849(21)00794-2. [Epub ahead of print]
    The role of mitochondrial reactive oxygen species in insulin resistance.
    Anita Ayer, Daniel J Fazakerley, David E James, Roland Stocker.
      Insulin resistance is one of the earliest pathological features of a suite of diseases including type 2 diabetes collectively referred to as metabolic syndrome. There is a growing body of evidence from both pre-clinical studies and human cohorts indicating that reactive oxygen species, such as the superoxide radical anion and hydrogen peroxide are key players in the development of insulin resistance. Here we review the evidence linking mitochondrial reactive oxygen species generated within mitochondria with insulin resistance in adipose tissue and skeletal muscle, two major insulin sensitive tissues. We outline the relevant mitochondria-derived reactive species, how the mitochondrial redox state is regulated, and methodologies available to measure mitochondrial reactive oxygen species. Importantly, we highlight key experimental issues to be considered when studying the role of mitochondrial reactive oxygen species in insulin resistance. Evaluating the available literature on both mitochondrial reactive oxygen species/redox state and insulin resistance in a variety of biological systems, we conclude that the weight of evidence suggests a likely role for mitochondrial reactive oxygen species in the etiology of insulin resistance in adipose tissue and skeletal muscle. However, major limitations in the methods used to study reactive oxygen species in insulin resistance as well as the lack of data linking mitochondrial reactive oxygen species and cytosolic insulin signaling pathways are significant obstacles in proving the mechanistic link between these two processes. We provide a framework to guide future studies to provide stronger mechanistic information on the link between mitochondrial reactive oxygen species and insulin resistance as understanding the source, localization, nature, and quantity of mitochondrial reactive oxygen species, their targets and downstream signaling pathways may pave the way for important new therapeutic strategies.
    Keywords:  Coenzyme Q; Hydrogen peroxide; Insulin resistance; Mitochondria; Redox signaling; Superoxide radical anion
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2021.11.007
  4. J Endocrinol. 2021 Nov 01. pii: JOE-21-0242.R1. [Epub ahead of print]
    Exercise does not improve insulin resistance and mitochondrial characteristics together.
    Amanda J Genders, Jujiao Kuang, Evelyn C Marin, Nicholas J Saner, Javier Botella, Macsue Jacques, Glenn K McConell, Victor A Andrade-Souza, Javier Chagolla, David J Bishop.
      The aim of this study was to investigate the relationship between mitochondrial content and respiratory function and whole-body insulin resistance in high fat diet (HFD) fed rats. Male Wistar rats were given either a chow diet or a HFD for 12 weeks. After four weeks of the dietary intervention, half of the rats in each group began eight weeks of interval training. In vivo glucose and insulin tolerance were assessed. Mitochondrial respiratory function was assessed in permeabilised soleus and white gastrocnemius (WG) muscles. Mitochondrial content was determined by measurement of citrate synthase (CS) activity and protein expression of components of the electron transport system (ETS). We found HFD rats had impaired glucose and insulin tolerance but increased mitochondrial respiratory function and increased protein expression of components of the ETS. This was accompanied by an increase in CS activity in WG. Exercise training improved glucose and insulin tolerance in the HFD rats. Mitochondrial respiratory function was increased with exercise training in the chow fed animals in soleus muscle. This exercise effect was absent in the HFD animals. In conclusion, exercise training improved insulin resistance in HFD rats, but without changes in mitochondrial respiratory function and content. The lack of an association between mitochondrial characteristics and whole-body insulin resistance was reinforced by the absence of strong correlations between these measures. Our results suggest that improvements in mitochondrial respiratory function and content are not responsible for improvements of whole-body insulin resistance in HFD rats.
    DOI:  https://doi.org/10.1530/JOE-21-0242
  5. Front Physiol. 2021 ;12 735932
    Skeletal Muscle Adaptations and Performance Outcomes Following a Step and Exponential Taper in Strength Athletes.
    S Kyle Travis, Kevin A Zwetsloot, Iñigo Mujika, Michael H Stone, Caleb D Bazyler.
      Before major athletic events, a taper is often prescribed to facilitate recovery and enhance performance. However, it is unknown which taper model is most effective for peaking maximal strength and positively augmenting skeletal muscle. Thus, the purpose of this study was to compare performance outcomes and skeletal muscle adaptations following a step vs. an exponential taper in strength athletes. Sixteen powerlifters (24.0 ± 4.0 years, 174.4 ± 8.2 cm, 89.8 ± 21.4 kg) participated in a 6-week training program aimed at peaking maximal strength on back squat [initial 1-repetition-maximum (1RM): 174.7 ± 33.4 kg], bench press (118.5 ± 29.9 kg), and deadlift (189.9 ± 41.2 kg). Powerlifters were matched based on relative maximal strength, and randomly assigned to either (a) 1-week overreach and 1-week step taper or (b) 1-week overreach and 3-week exponential taper. Athletes were tested pre- and post-training on measures of body composition, jumping performance, isometric squat, and 1RM. Whole muscle size was assessed at the proximal, middle, and distal vastus lateralis using ultrasonography and microbiopsies at the middle vastus lateralis site. Muscle samples (n = 15) were analyzed for fiber size, fiber type [myosin-heavy chain (MHC)-I, -IIA, -IIX, hybrid-I/IIA] using whole muscle immunohistochemistry and single fiber dot blots, gene expression, and microRNA abundance. There were significant main time effects for 1RM squat (p < 0.001), bench press (p < 0.001), and deadlift, (p = 0.024), powerlifting total (p < 0.001), Wilks Score (p < 0.001), squat jump peak-power scaled to body mass (p = 0.001), body mass (p = 0.005), fat mass (p = 0.002), and fat mass index (p = 0.002). There were significant main time effects for medial whole muscle cross-sectional area (mCSA) (p = 0.006) and averaged sites (p < 0.001). There was also a significant interaction for MHC-IIA fiber cross-sectional area (fCSA) (p = 0.014) with post hoc comparisons revealing increases following the step-taper only (p = 0.002). There were significant main time effects for single-fiber MHC-I% (p = 0.015) and MHC-IIA% (p = 0.033), as well as for MyoD (p = 0.002), MyoG (p = 0.037), and miR-499a (p = 0.033). Overall, increases in whole mCSA, fCSA, MHC-IIA fCSA, and MHC transitions appeared to favor the step taper group. An overreach followed by a step taper appears to produce a myocellular environment that enhances skeletal muscle adaptations, whereas an exponential taper may favor neuromuscular performance.
    Keywords:  fiber typing; gene expression; mRNA; maximal strength; muscle biopsy; myosin heavy chain; powerlifting; resistance training
    DOI:  https://doi.org/10.3389/fphys.2021.735932
  6. Physiology (Bethesda). 2021 Nov 15.
    Insulin, Muscle Glucose Uptake, and Hexokinase: Revisiting the Road Not Taken.
    David H Wasserman.
      Research conducted over the last 50 years has provided insight into the mechanisms by which insulin stimulates glucose transport across the skeletal muscle cell membrane. Transport alone, however, does not result in net glucose uptake as freeglucose equilibrates across the cell membrane and is not metabolized. Glucose uptake requires that glucose is phosphorylated by hexokinases. Phosphorylated glucosecannot leave the cell and is the substrate for metabolism. It is indisputable that glucose phosphorylation is essential for glucose uptake. Major advances have been made in defining the regulation of the insulin-stimulated glucose transporter, GLUT4, in skeletalmuscle. By contrast, the insulin-regulated hexokinase, hexokinase II parallels RobertFrost's Road Not Taken. Here the case is made that an understanding of glucosephosphorylation by hexokinase II is necessary to define the regulation of skeletal muscle glucose uptake in health and insulin resistance. Results of studies from different physiological disciplines that have elegantly described how hexokinase II can beregulated are summarized to provide a framework for potential application to skeletal muscle. Mechanisms by which hexokinase II is regulated in skeletal muscle await rigorous examination.
    Keywords:  GLUT4; glucose; hexokinase; insulin; muscle
    DOI:  https://doi.org/10.1152/physiol.00034.2021
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