bims-exemet Biomed News
on Exercise metabolism
Issue of 2021‒04‒04
fourteen papers selected by
Javier Botella Ruiz
Victoria University

  1. J Physiol. 2021 Mar 26.
      KEY POINTS: Muscle glycogen and intramuscular triglycerides (IMTG, stored in lipid droplets) are important energy substrates during prolonged exercise. Exercise-induced changes in lipid droplet (LD) morphology (i.e., LD size and number) has not yet been studied under nutritional conditions typically adopted by elite endurance athletes, that is, after carbohydrate (CHO) loading and CHO feeding during exercise. We report for the first time that exercise reduces IMTG content in both central and peripheral regions of type I and IIa fibres, reflective of decreased LD number in both fibre types whereas reductions in LD size was exclusive to type I fibres. Additionally, CHO feeding does not alter subcellular IMTG utilisation, LD morphology or muscle glycogen utilisation in type I or IIa/II fibres. In the absence of alterations to muscle fuel selection, CHO feeding does not attenuate cell signalling with regulatory roles in mitochondrial biogenesis.ABSTRACT: We examined the effects of carbohydrate (CHO) feeding on lipid droplet (LD) morphology, muscle glycogen utilisation and exercise-induced skeletal muscle cell signalling. After a 36 h CHO loading protocol and pre-exercise meal (12 and 2 g·kg-1 , respectively), eight trained males ingested 0, 45 or 90 g CHO·h-1 during 180 min cycling at lactate threshold followed by an exercise capacity test (150% lactate threshold). Muscle biopsies were obtained pre- and post-completion of submaximal exercise. Exercise decreased (P<0.01) glycogen concentration to comparable levels (∼700 to 250 mmol·kg-1 dw), though utilisation was greater in type I (∼40%) versus type II fibres (∼10%) (P<0.01). LD content decreased in type I (∼50%) and type IIa fibres (∼30%) (P<0.01) with greater utilisation in type I fibres (P<0.01). CHO feeding did not affect glycogen or IMTG utilisation in type I or II fibres (all P>0.05). Exercise decreased LD number within central and peripheral regions of both type I and IIa fibres, though reduced LD size was exclusive to type I fibres. Exercise induced (all P<0.05) comparable AMPKThr172 (∼4 fold), p53Ser15 (∼2 fold) and CaMKIIThr268 phosphorylation (∼2 fold) with no effects of CHO feeding (all P>0.05). CHO increased exercise capacity where 90 g·h-1 (233 ± 133 s) > 45 g·h-1 (156 ± 66 s; P = 0.06) > 0 g·h-1 (108 ± 54 s; P = 0.03). In conditions of high pre-exercise CHO availability, we conclude CHO feeding does not influence exercise-induced changes in LD morphology, glycogen utilisation or cell signalling pathways with regulatory roles in mitochondrial biogenesis. This article is protected by copyright. All rights reserved.
    Keywords:  glycogen; intramuscular triglyceride; vastus lateralis
  2. FASEB J. 2021 May;35(5): e21499
      The microvasculature is important for both health and exercise tolerance in a range of populations. However, methodological limitations have meant changes in microvascular blood flow are rarely assessed in humans during interventions designed to affect skeletal muscle blood flow such as the wearing of compression garments. The aim of this study is, for the first time, to use contrast-enhanced ultrasound to directly measure the effects of compression on muscle microvascular blood flow alongside measures of femoral artery blood flow and muscle oxygenation following intense exercise in healthy adults. It was hypothesized that both muscle microvascular and femoral artery blood flows would be augmented with compression garments as compared with a control condition. Ten recreationally active participants completed two repeated-sprint exercise sessions, with and without lower-limb compression tights. Muscle microvascular blood flow, femoral arterial blood flow (2D and Doppler ultrasound), muscle oxygenation (near-infrared spectroscopy), cycling performance, and venous blood samples were measured/taken throughout exercise and the 1-hour post-exercise recovery period. Compared with control, compression reduced muscle microvascular blood volume and attenuated the exercise-induced increase in microvascular velocity and flow immediately after exercise and 1 hour post-exercise. Compression increased femoral artery diameter and augmented the exercise-induced increase in femoral arterial blood flow during exercise. Markers of blood oxygen extraction in muscle were increased with compression during and after exercise. Compression had no effect on blood lactate, glucose, or exercise performance. We provide new evidence that lower-limb compression attenuates the exercise-induced increase in skeletal muscle microvascular blood flow following exercise, despite a divergent increase in femoral artery blood flow. Decreased muscle microvascular perfusion is offset by increased muscle oxygen extraction, a potential mechanism allowing for the maintenance of exercise performance.
    Keywords:  NIRS; capillary-myocyte interface; ergogenic; microvasculature; sprint-interval exercise
  3. J Physiol Biochem. 2021 Mar 31.
      Skeletal muscle atrophy (SMA) is a dominant symptom induced by estrogen deficiency which can lead to severe health problems of postmenopausal women. Furthermore, estrogen deficiency has severely compromised the maintenance of muscle stem cells as well as impairs self-renewal and differentiation into muscle fibers. Resistance training is commonly considered as a positive and useful intervention in accelerating the rate of muscle growth. As one of the resistance training, whether the weight-bearing exercise can alleviate SMA induced by estrogen deficiency has not been investigated. The rats were divided into 3 groups randomly: sham group, ovariectomized (OVX) group, and weight-bearing exercise (WBE) therapeutic group. The weight that rats were loaded was 35% of their body weight, and the rats were trained by treadmill training (5° slope, 20 m/min, 30 min/day, 6 days/week) for 8 weeks. After training, the quality and strength of skeletal muscle of the WBE rats were improved; meanwhile, the cross-sectional areas of the skeletal muscle were also increased. Moreover, the WBE activated Akt significantly, upregulated the expression of mTOR, and downregulated the expression of MSTN and its receptor ActRIIB and FoxO1, respectively. The SMA phenomena of rats which induced by estrogen deficiency were prevented effectively via WBE, and the MSTN/Akt/mTOR and FoxO1 signaling pathway may be the predominant way in this improvement.
    Keywords:  Skeletal muscle atrophy,·Estrogen deficiency,·Ovariectomized rats,·Myostatin,·Signaling pathway; Weight-bearing exercise
  4. Antioxidants (Basel). 2021 Mar 30. pii: 537. [Epub ahead of print]10(4):
      Physical exercise represents a major challenge to whole-body homeostasis, provoking acute and adaptative responses at the cellular and systemic levels. Different sources of reactive oxygen species (ROS) have been described in skeletal muscle (e.g., NADPH oxidases, xanthine oxidase, and mitochondria) and are closely related to the physiological changes induced by physical exercise through the modulation of several signaling pathways. Many signaling pathways that are regulated by exercise-induced ROS generation, such as adenosine monophosphate-activated protein kinase (AMPK), mitogen activated protein kinase (MAPK), nuclear respiratory factor2 (NRF2), and PGC-1α are involved in skeletal muscle responses to physical exercise, such as increased glucose uptake, mitochondriogenesis, and hypertrophy, among others. Most of these adaptations are blunted by antioxidants, revealing the crucial role played by ROS during and after physical exercise. When ROS generation is either insufficient or exacerbated, ROS-mediated signaling is disrupted, as well as physical exercise adaptations. Thus, an understanding the limit between "ROS that can promote beneficial effects" and "ROS that can promote harmful effects" is a challenging question in exercise biology. The identification of new mediators that cause reductive stress and thereby disrupt exercise-stimulated ROS signaling is a trending on this topic and are covered in this current review.
    Keywords:  NADPH oxidase; ROS; exercise; oxidative stress; redox signaling; reductive stress; skeletal muscle
  5. Nutr Metab Cardiovasc Dis. 2021 Jan 27. pii: S0939-4753(21)00008-9. [Epub ahead of print]
      BACKGROUND AND AIMS: It has been demonstrated that maternal low protein during development induces mitochondrial dysfunction and oxidative stress in the heart. Moderate-intensity exercise in early life, conversely, increases the overall cardiac health. Thus, we hypothesize that moderate-intensity exercise performed during young age could ameliorate the deleterious effect of maternal protein deprivation on cardiac bioenergetics.METHODS AND RESULTS: We used a rat model of maternal protein restriction during gestational and lactation period followed by an offspring treadmill moderate physical training. Pregnant rats were divided into two groups: normal nutrition receiving 17% of casein in the diet and undernutrition receiving a low-protein diet (8% casein). At 30 days of age, the male offspring were further subdivided into sedentary (NS and LS) or exercised (NT and LT) groups. Treadmill exercise was performed as follows: 4 weeks, 5 days/week, 60 min/day at 50% of maximal running capacity. Our results showed that a low-protein diet decreases oxidative metabolism and mitochondrial function associated with higher oxidative stress. In contrast, exercise rescues mitochondrial capacity and promotes a cellular resilience to oxidative stress. Up-regulation of cardiac sirtuin 1 and 3 decreased acetylation levels, redeeming from the deleterious effect of protein restriction.
    CONCLUSION: Our findings show that moderate daily exercise during a young age acts as a therapeutical intervention opposing the harmful effects of a maternal diet restricted in protein.
    Keywords:  Childhood exercise; Epigenetic; Heart; Maternal low-protein diet; Oxidative stress
  6. Int J Mol Sci. 2021 Mar 08. pii: 2741. [Epub ahead of print]22(5):
      The regulation of skeletal muscle mass and organelle homeostasis is dependent on the capacity of cells to produce proteins and to recycle cytosolic portions. In this investigation, the mechanisms involved in skeletal muscle mass regulation-especially those associated with proteosynthesis and with the production of new organelles-are presented. Thus, the critical roles of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) pathway and its regulators are reviewed. In addition, the importance of ribosome biogenesis, satellite cells involvement, myonuclear accretion, and some major epigenetic modifications related to protein synthesis are discussed. Furthermore, several studies conducted on the topic of exercise training have recognized the central role of both endurance and resistance exercise to reorganize sarcomeric proteins and to improve the capacity of cells to build efficient organelles. The molecular mechanisms underlying these adaptations to exercise training are presented throughout this review and practical recommendations for exercise prescription are provided. A better understanding of the aforementioned cellular pathways is essential for both healthy and sick people to avoid inefficient prescriptions and to improve muscle function with emergent strategies (e.g., hypoxic training). Finally, current limitations in the literature and further perspectives, notably on epigenetic mechanisms, are provided to encourage additional investigations on this topic.
    Keywords:  DNA methylation; eIF3f; endurance training; epigenetic modifications; hypoxia; mTOR; protein turnover; resistance training; ribosome biogenesis; satellite cells
  7. Appl Physiol Nutr Metab. 2021 Mar 27.
      We investigated the effects of the acute and chronic exercise, prescribed in different intensity zones, but with total load-matched on mitochondrial markers (COX-IV, Tfam, and citrate synthase (CS) activity in skeletal muscles, heart, and liver), glycogen stores, aerobic capacity and anaerobic index in swimming rats. For this, two experimental designs were performed (acute and chronic efforts). Load-matched exercises were prescribed below and above and on the anaerobic threshold (AnT), determined by the Lactate Minimum test. In chronic programs, two training prescription strategies were assessed (monotonous and linear periodized model). Results show changes in glycogen stores but no modification in the COX-IV and Tfam contents after acute exercises. In the chronic protocols, COX-IV and Tfam proteins and CS adaptations were intensity and tissue dependents. Monotonous training promoted better adaptations than the periodized model. Training at 80% of the AnT improved both performance variables, emphasizing the anaerobic index, concomitant to CS and COX-IV improvement (soleus muscle). The aerobic capacity and CS activity (gastrocnemius) were increased after 120% AnT training. In conclusion, acute exercise protocol did not promote responses in mitochondrial target proteins. An intensity and tissue dependence are reported in the chronic protocols, highlighting training at 80 and 120% of the AnT. Novelty: • Load-matched acute exercise did not enhance COX-IV and Tfam contents in skeletal muscles, heart, and liver. • In chronic exercise, COX-IV, Tfam, and citrate synthase activity adaptations were intensity and tissue dependents. •Monotonous training was more efficient than the periodized linear model in adaptations of target proteins and enzymatic activity.
  8. Biology (Basel). 2021 Mar 02. pii: 181. [Epub ahead of print]10(3):
      Numerous studies have shown that cf nDNA significantly rises in stress caused by exercise. However, during nuclear decondensation, released DNA is followed by histones. Histones are also a common disease marker. After PAD4 mediated hypercitrullination extracellular H3Cit exhibits high toxicity contributing to tissue damage which, in cases of systemic inflammation, may lead to multiorgan failure and finally to death. We tested whether circulating histones rise in response to strenuous exercise. Eleven average-trained men performed three treadmill exercise tests to exhaustion at speed corresponding to 70% VO2max separated by 72 h of resting. Blood was collected before and just after each bout of exercise and plasma proteins were measured using enzyme-linked immunosorbent assay, whereas platelet activity was estimated with Light Transmission Aggregometry. Both, circulating histones and PAD4 raised in response to exercise. Plasma citrullinated histones increased from 3.1 ng/mL to 5.96 ng/mL (p = 0.0059), from 3.65 ng/mL to 6.37 ng/mL (p = 0.02), and from 3.86 ng/mL to 4.75 ng/mL (p = 0.033) after the first, second, and third treadmill run, respectively. However despite the parallel increase, no significant correlation between citrullinated histone and aggregation or cell-free nDNA was found. Furthermore, positive correlations of cf nDNA with aggregation and PAD4, lactate with aggregation, and lactate with citrullinated histone have been observed.
    Keywords:  PAD4; aggregation; cell-free DNA; exercise; histone h3; interleukins
  9. Redox Biol. 2021 Mar 24. pii: S2213-2317(21)00104-X. [Epub ahead of print] 101956
      Research in redox biology of exercise has made considerable advances in the last 70 years. Since the seminal study of George Pake's group calculating the content of free radicals in skeletal muscle in resting conditions in 1954, many discoveries have been made in the field. The first section of this review is devoted to highlight the main research findings and fundamental changes in the exercise redox biology discipline. It includes: i) the first steps in free radical research, ii) the relation between exercise and oxidative damage, iii) the redox regulation of muscle fatigue, iv) the sources of free radicals during muscle contractions, and v) the role of reactive oxygen species as regulators of gene transcription and adaptations in skeletal muscle. In the second section of the manuscript, we review the available biomarkers for assessing health, performance, recovery during exercise training and overtraining in the sport population. Among the set of biomarkers that could be determined in exercise studies we deepen on the four categories of redox biomarkers: i) oxidants, ii) antioxidants, iii) oxidation products (markers of oxidative damage), and iv) measurements of the redox balance (markers of oxidative stress). The main drawbacks, strengths, weaknesses, and methodological considerations of every biomarker are also discussed.
    Keywords:  Antioxidants; Biomarkers; Exercise; Free radical; Oxidative stress
  10. Nature. 2021 Apr;592(7852): S7-S9
    Keywords:  Cell biology; Physiology
  11. Metabolites. 2021 Mar 07. pii: 151. [Epub ahead of print]11(3):
      Dynamic changes in circulating and tissue metabolites and lipids occur in response to exercise-induced cellular and whole-body energy demands to maintain metabolic homeostasis. The metabolome and lipidome in a given biological system provides a molecular snapshot of these rapid and complex metabolic perturbations. The application of metabolomics and lipidomics to map the metabolic responses to an acute bout of aerobic/endurance or resistance exercise has dramatically expanded over the past decade thanks to major analytical advancements, with most exercise-related studies to date focused on analyzing human biofluids and tissues. Experimental and analytical considerations, as well as complementary studies using animal model systems, are warranted to help overcome challenges associated with large human interindividual variability and decipher the breadth of molecular mechanisms underlying the metabolic health-promoting effects of exercise. In this review, we provide a guide for exercise researchers regarding analytical techniques and experimental workflows commonly used in metabolomics and lipidomics. Furthermore, we discuss advancements in human and mammalian exercise research utilizing metabolomic and lipidomic approaches in the last decade, as well as highlight key technical considerations and remaining knowledge gaps to continue expanding the molecular landscape of exercise biology.
    Keywords:  exercise; lipidome; lipidomics; mass spectrometry; metabolism; metabolome; metabolomics; nuclear magnetic resonance; omics
  12. Nutrients. 2021 Mar 24. pii: 1056. [Epub ahead of print]13(4):
      Iron deficiency (ID), with or without anemia, is responsible for physical fatigue. This effect may be linked to an alteration of mitochondrial metabolism. Our aim was to assess the impact of ID on skeletal striated muscle mitochondrial metabolism. Iron-deficient non-anemic mice, obtained using a bloodletting followed by a low-iron diet for three weeks, were compared to control mice. Endurance was assessed using a one-hour submaximal exercise on a Rotarod device and activities of mitochondrial complexes I and IV were measured by spectrophotometry on two types of skeletal striated muscles, the soleus and the quadriceps. As expected, ID mice displayed hematologic markers of ID and reduced iron stores, although none of them were anemic. In ID mice, endurance was significantly reduced and activity of the respiratory chain complex I, normalized to citrate synthase activity, was significantly reduced in the soleus muscle but not in the quadriceps. Complex IV activities were not significantly different, neither in the soleus nor in the quadriceps. We conclude that ID without anemia is responsible for impaired mitochondrial complex I activity in skeletal muscles with predominant oxidative metabolism. These results bring pathophysiological support to explain the improved physical activity observed when correcting ID in human. Further studies are needed to explore the mechanisms underlying this decrease in complex I activity and to assess the role of iron therapy on muscle mitochondrial metabolism.
    Keywords:  complex I; fatigue; iron deficiency; mitochondrial metabolism; physical capacity; striated skeletal muscle
  13. Int J Mol Sci. 2021 Mar 18. pii: 3110. [Epub ahead of print]22(6):
      Cachexia is a multifactorial syndrome characterized by muscle loss that cannot be reversed by conventional nutritional support. To uncover the molecular basis underlying the onset of cancer cachectic muscle wasting and establish an effective intervention against muscle loss, we used a cancer cachectic mouse model and examined the effects of aerobic exercise. Aerobic exercise successfully suppressed muscle atrophy and activated adiponectin signaling. Next, a cellular model for cancer cachectic muscle atrophy using C2C12 myotubes was prepared by treating myotubes with a conditioned medium from a culture of colon-26 cancer cells. Treatment of the atrophic myotubes with recombinant adiponectin was protective against the thinning of cells through the increased production of p-mTOR and suppression of LC3-II. Altogether, these findings suggest that the activation of adiponectin signaling could be part of the molecular mechanisms by which aerobic exercise ameliorates cancer cachexia-induced muscle wasting.
    Keywords:  adiponectin; aerobic exercise; cancer cachexia; muscle atrophy