bims-misrem Biomed News
on Mitochondria and sarcoplasmic reticulum in muscle mass
Issue of 2021‒04‒25
five papers selected by
Rafael Antonio Casuso Pérez
University of Granada

  1. Med Sci Sports Exerc. 2021 Apr 15.
      INTRODUCTION: Whether short-term, single-mode exercise training can improve physical fitness prior to a period of reduced physical activity (e.g. post-surgery recovery) is not well characterized in clinical populations nor middle-age adults. We investigated skeletal muscle adaptive responses following endurance exercise training (ENT), high-intensity interval training (HIIT) or resistance exercise training (RET), and a subsequent period of detraining, in sedentary, middle-age men.METHODS: Thirty-five sedentary, males (39±3 yr) were randomized to parallel groups and undertook six weeks of either ENT (n=12), HIIT (n=12) or RET (n=11) followed by 2.5 weeks of detraining. Skeletal muscle fiber characteristics, body composition, muscle thickness, muscle strength, aerobic capacity, resting energy expenditure and glucose homeostasis were assessed at baseline, and after exercise training and detraining.
    RESULTS: Lean mass increased after RET and HIIT (+3.2±1.6% and +1.6±2.1%, P<0.05). Muscle strength (sum of leg press, leg extension and bench press 1RMs) increased after all training interventions (RET: +25±5%; HIIT: +10±5%; ENT: +7±7%, P<0.05). Aerobic capacity increased only after HIIT and ENT (+14±7% and +11±11%, P<0.05). Type I and II muscle fiber size increased for all groups post-training (main effect of time, P<0.05). Following a period of detraining, the gains in lean mass and maximal muscle strength were maintained in RET and HIIT groups, but maximal aerobic capacity declined below post-training levels in HIIT and ENT (P<0.05).
    CONCLUSION: Six weeks of HIIT induced widespread adaptations prior to detraining in middle-age men. Exercise training-induced increases in aerobic capacity declined during 2.5 weeks of detraining but gains in lean mass and muscle strength were maintained.
  2. Cell Rep. 2021 Apr 20. pii: S2211-1247(21)00332-6. [Epub ahead of print]35(3): 109018
      Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.
    Keywords:  DAMP; exercise training; heme; heme oxygenase-1; hemopexin; mitochondrial dysfunction; muscle atrophy; muscle microtrauma; satellite cells
  3. Life Sci. 2021 Apr 14. pii: S0024-3205(21)00496-3. [Epub ahead of print] 119511
      Effective Ca2+ dependent mitochondrial energy supply is imperative for proper cardiac contractile activity, while disruption of Ca2+ homeostasis participates in the pathogenesis of multiple human diseases. This phenomenon is particularly prominent in cardiac ischemia and reperfusion (I/R) and heart failure, both of which require strict clinical intervention. The interface between endoplasmic reticula (ER) and mitochondria, designated the mitochondria-associated membrane (MAM), is now regarded as a crucial mediator of Ca2+ transportation. Thus, interventions targeting this physical and functional coupling between mitochondria and the ER are highly desirable. Increasing evidence supports the notion that restoration, and maintenance, of the physiological contact between these two organelles can improve mitochondrial function, while inhibiting cell death, thereby sufficiently ameliorating I/R injury and heart failure development. A better understanding regarding the underlying mechanism of MAM-mediated transport will pave the way for identification of novel treatment approaches for heart disease. Therefore, in this review, we summarize the crucial functions and potential mechanisms of MAMs in the pathogenesis of I/R and heart failure.
    Keywords:  Calcium transfer; Heart failure; Mitochondria; Mitochondria-associated membranes; Myocardial ischemia-reperfusion injury
  4. Am J Physiol Endocrinol Metab. 2021 Apr 05.
      Elevated mitochondrial H2O2 emission and an oxidative shift in cytosolic redox environment have been linked to high fat diet-induced insulin resistance in skeletal muscle. To test specifically whether increased flux through mitochondrial fatty acid oxidation, in the absence of elevated energy demand, directly alters mitochondrial function and redox state in muscle, two genetic models characterized by increased muscle β-oxidation flux were studied. In mice overexpressing peroxisome proliferator activated receptor-α in muscle (MCK-PPARα), lipid supported mitochondrial respiration, membrane potential (ΔΨm) and H2O2 production rate (JH2O2) were increased, which coincided with a more oxidized cytosolic redox environment, reduced muscle glucose uptake, and whole-body glucose intolerance despite an increased rate of energy expenditure. Similar results were observed in lipin-1 deficient, fatty-liver dystrophic mice, another model characterized by increased β-oxidation flux and glucose intolerance. Crossing MCAT (mitochondrial-targeted catalase) with MCK-PPARα mice normalized JH2O2 production, redox environment and glucose tolerance, but surprisingly both basal and absolute insulin-stimulated rates of glucose uptake in muscle remained depressed. Also surprising, when placed on a high fat diet MCK-PPARα mice were characterized by much lower whole body, fat and lean mass as well as improved glucose tolerance relative to wild-type mice, providing additional evidence that overexpression of PPARα in muscle imposes more extensive metabolic stress than experienced by wild-type mice on a high fat diet. Overall, the findings suggest that driving an increase in skeletal muscle fatty acid oxidation in the absence of metabolic demand imposes mitochondrial reductive stress and elicits multiple counterbalance metabolic responses in attempt to restore bioenergetic homeostasis.
    Keywords:  fat oxidation; glucose tolerance; insulin resistance; mitochondria; skeletal muscle
  5. J Appl Physiol (1985). 2021 Apr 22.
      While it has long been known that contraction robustly stimulates skeletal muscle glucose uptake, the molecular steps regulating this increase remain incompletely defined. The mammalian ortholog of Sir2, sirtuin 1 (SIRT1), is an NAD+-dependent protein deacetylase that is thought to link perturbations in energy flux associated with exercise to subsequent cellular adaptations. Nevertheless, its role in contraction-stimulated glucose uptake has not been described. The objective of this study was to determine the importance of SIRT1 to contraction-stimulated glucose uptake in mouse skeletal muscle. Using a radioactive 2-deoxyglucose uptake (2DOGU) approach, we measured ex vivo glucose uptake in unstimulated (rested) and electrically-stimulated (100 Hz contraction every 15s for 10 min; contracted) extensor digitorum longus (EDL) and soleus from ~15 week old male and female mice with muscle-specific knockout of SIRT1 deacetylase activity (mKO) and their wildtype (WT) littermates. Skeletal muscle force decreased over the contraction protocol, although there were no differences in the rate of fatigue between genotypes. In EDL and soleus, depletion of SIRT1 deacetylase activity did not affect contraction-induced increase in glucose uptake in either sex. Interestingly, the absolute rate of contraction-stimulated 2DOGU was ~1.4-fold higher in female compared to male mice, regardless of muscle type. Taken together, our findings demonstrate that SIRT1 is not required for contraction-stimulated glucose uptake in mouse skeletal muscle. Moreover, to our knowledge, this is the first demonstration of sex-based differences in contraction-stimulated glucose uptake in mouse skeletal muscle.
    Keywords:  2-deoxyglucose; deacetylase; exercise; sex dimorphism