bims-exemet Biomed News
on Exercise metabolism
Issue of 2021–06–06
eleven papers selected by
Javier Botella Ruiz, Victoria University



  1. J Cachexia Sarcopenia Muscle. 2021 May 31.
       BACKGROUND: Declines in cardiorespiratory fitness (CRF) and fat-free mass (FFM) with age are linked to mortality, morbidity and poor quality of life. High-intensity interval training (HIIT) has been shown to improve CRF and FFM in many groups, but its efficacy in the very old, in whom comorbidities are present is undefined. We aimed to assess the efficacy of and physiological/metabolic responses to HIIT, in a cohort of octogenarians with comorbidities (e.g. hypertension and osteoarthritis).
    METHODS: Twenty-eight volunteers (18 men, 10 women, 81.2 ± 0.6 years, 27.1 ± 0.6 kg·m-2 ) with American Society of Anaesthesiology (ASA) Grade 2-3 status each completed 4 weeks (12 sessions) HIIT after a control period of equal duration. Before and after each 4 week period, subjects underwent body composition assessments and cardiopulmonary exercise testing. Quadriceps muscle biopsies (m. vastus lateralis) were taken to quantify anabolic signalling, mitochondrial oxidative phosphorylation, and cumulative muscle protein synthesis (MPS) over 4-weeks.
    RESULTS: In comorbid octogenarians, HIIT elicited improvements in CRF (anaerobic threshold: +1.2 ± 0.4 ml·kg-1 ·min-1 , P = 0.001). HIIT also augmented total FFM (47.2 ± 1.4 to 47.6 ± 1.3 kg, P = 0.04), while decreasing total fat mass (24.8 ± 1.3 to 24 ± 1.2 kg, P = 0.0002) and body fat percentage (33.1 ± 1.5 to 32.1 ± 1.4%, P = 0.0008). Mechanistically, mitochondrial oxidative phosphorylation capacity increased after HIIT (i.e. citrate synthase activity: 52.4 ± 4 to 67.9 ± 5.1 nmol·min-1 ·mg-1 , P = 0.005; membrane protein complexes (C): C-II, 1.4-fold increase, P = 0.002; C-III, 1.2-fold increase, P = 0.03), as did rates of MPS (1.3 ± 0.1 to 1.5 ± 0.1%·day-1 , P = 0.03). The increase in MPS was supported by up-regulated phosphorylation of anabolic signalling proteins (e.g. AKT, p70S6K, and 4E-BP1; all P < 0.05). There were no changes in any of these parameters during the control period. No adverse events were reported throughout the study.
    CONCLUSIONS: The HIIT enhances skeletal muscle mass and CRF in octogenarians with disease, with up-regulation of MPS and mitochondrial capacity likely underlying these improvements. HIIT can be safely delivered to octogenarians with disease and is an effective, time-efficient intervention to improve muscle mass and physical function in a short time frame.
    Keywords:  Ageing; Disease; Exercise; HIIT; Muscle; Protein synthesis
    DOI:  https://doi.org/10.1002/jcsm.12724
  2. Curr Mol Pharmacol. 2021 May 21.
       BACKGROUND: Diabetes mellitus (DM) affects the musculoskeletal system through its metabolic perturbations. Exercise modulates blood sugar levels and increases the body's sensitivity to insulin in patients with DM.
    OBJECTIVE: This study aimed to investigate the potential effects of combined quercetin and coenzyme Q10 (CoQ10) supplements with or without exercise on the histological, biochemical and molecular structures of diabetic rat's skeletal muscle.
    METHOD: A total of 64 adult male albino rats were divided into six groups: control, trained nondiabetic, non-trained diabetic, diabetic rats treated with combined CoQ10 and quercetin, diabetic rats with treadmill training, and diabetic rats treated with treadmill training and CoQ10 and quercetin. Blood and skeletal muscle samples were obtained from all groups for routine histological examination and biochemical determination of cytokine levels and protein activities. Quantitative real-time polymerase chain reaction (qRT-PCR) and morphometric analysis of PAS and Bax expressions were also performed.
    RESULTS: Biochemical analysis revealed improvement in all studied parameters with combined CoQ10 and quercetin than exercise training alone. Combined treatment and exercise showed significant improvement in all parameters especially interleukin 6 and malondialdehyde. Fibronectin type III domain-containing protein 5 (FNDC5) expression and irisin levels increased in all trained groups but combined treatment with exercise significantly increased their levels than exercise alone. Histological analysis revealed improvement after exercise or combined treatment; however, when exercise was combined with CoQ10 and quercetin, marked improvement was observed.
    CONCLUSION: the combination of CoQ10 and quercetin could be promising in preserving musculoskeletal function in patients with DM concomitantly with physical exercise.
    Keywords:  Diabetes Mellitus; Exercise; Irisin.; Quercetin; Skeletal Muscle; coenzyme Q10
    DOI:  https://doi.org/10.2174/1874467214666210521170339
  3. Front Physiol. 2021 ;12 656909
      Skeletal muscle (SM) tissue has been repetitively shown to play a major role in whole-body glucose homeostasis and overall metabolic health. Hence, SM hypertrophy through resistance training (RT) has been suggested to be favorable to glucose homeostasis in different populations, from young healthy to type 2 diabetic (T2D) individuals. While RT has been shown to contribute to improved metabolic health, including insulin sensitivity surrogates, in multiple studies, a universal understanding of a mechanistic explanation is currently lacking. Furthermore, exercised-improved glucose homeostasis and quantitative changes of SM mass have been hypothesized to be concurrent but not necessarily causally associated. With a straightforward focus on exercise interventions, this narrative review aims to highlight the current level of evidence of the impact of SM hypertrophy on glucose homeostasis, as well various mechanisms that are likely to explain those effects. These mechanistic insights could provide a strengthened rationale for future research assessing alternative RT strategies to the current classical modalities, such as low-load, high repetition RT or high-volume circuit-style RT, in metabolically impaired populations.
    Keywords:  insulin sensitivity; muscle capillarization; muscle hypertrophy; muscle mass; muscle mitochondrial activity; muscle mitochondrial biogenesis; muscle quality; resistance training
    DOI:  https://doi.org/10.3389/fphys.2021.656909
  4. Metabolites. 2021 May 18. pii: 323. [Epub ahead of print]11(5):
      Sarcopenia is an aging-induced syndrome characterized by a progressive reduction of skeletal muscle mass and strength. Increasing evidence has attested that appropriate and scientific exercise could induce autophagy or optimize the functional status of autophagy, which plays a critical role in senescent muscular dystrophy. As a publicly recognized strategy for extending lifespan and improving the health of the elderly, the underlying mechanisms of lifelong regular aerobic exercise for the prevention of sarcopenia have not been fully elucidated. To explore the role of lifelong aerobic exercise in the beneficial regulation of autophagic signaling pathways in senescent skeletal muscle, the natural aging mice were used as the sarcopenia model and subjected to lifelong treadmill running to evaluate corresponding parameters related to skeletal muscle atrophy and autophagic signaling pathways. Compared with the young control mice, the aged mice showed a significant reduction in skeletal muscle mass, gastrocnemius muscle weight/body weight (GMW/BW) ratio, and cross-sectional areas (CSA) of skeletal muscle fibers (p < 0.01). In contrast, lifelong aerobic exercise effectively rescued these reduced biomarkers associated with muscle atrophy. Moreover, as shown in the activated AMPK/PGC-1α signaling pathway, lifelong aerobic exercise successfully prevented the aging-induced impairment of the ubiquitin-proteasome system (UPS), excessive apoptosis, defective autophagy, and mitochondrial dysfunction. The exercise-induced autophagy suppressed the key regulatory components of the UPS, inhibited excessive apoptosis, and optimized mitochondrial quality control, thereby preventing and delaying aging-induced skeletal muscle atrophy.
    Keywords:  apoptosis; autophagy; lifelong aerobic exercise; mitochondrial quality control; sarcopenia; ubiquitin-proteasome system
    DOI:  https://doi.org/10.3390/metabo11050323
  5. Healthcare (Basel). 2021 May 22. pii: 618. [Epub ahead of print]9(6):
       BACKGROUND: Monocytes are critical components, not only for innate immunity, but also for the activation of the adaptive immune system. Many studies in animals and humans have demonstrated that monocytes may be closely associated with chronic inflammatory diseases and be proved to be pivotal in the association between high-intensity exercise and anti-inflammation response. However, the underlying molecular mechanisms driving this are barely understood. The present study aimed to screen for potential hub genes and candidate signaling pathways associated with the effects of high-intensity exercise on human monocytes through bioinformatics analysis.
    MATERIALS AND METHODS: The GSE51835 gene expression dataset was downloaded from the Gene Expression Omnibus database. The dataset consists of 12 monocyte samples from two groups of pre-exercise and post-exercise individuals. Identifying differentially expressed genes (DEGs) with R software, and functional annotation and pathway analyses were then performed with related web databases. Subsequently, a protein-protein interaction (PPI) network which discovers key functional protein and a transcription factors-DEGs network which predicts upstream regulators were constructed.
    RESULTS: A total of 146 differentially expressed genes were identified, including 95 upregulated and 51 downregulated genes. Gene Ontology analysis indicated that in the biological process functional group, these DEGs were mainly involved in cellular response to hydrogen peroxide, response to unfolded protein, negative regulation of cell proliferation, cellular response to laminar fluid shear stress, and positive regulation of protein metabolic process. The top five enrichment pathways in a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were the FoxO signaling pathway, protein processing in the endoplasmic reticulum, influenza A, the ErbB signaling pathway, and the MAPK signaling pathway. TNF, DUSP1, ATF3, CXCR4, NR4A1, BHLHE40, CDKN1B, SOCS3, TNFAIP3, and MCL1 were the top 10 potential hub genes. The most important modules obtained in the PPI network were performed KEGG pathway analysis, which showed that these genes were mainly involved in the MAPK signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, osteoclast differentiation, and apoptosis. A transcription factor (TF) target network illustrated that FOXJ2 was a critical regulatory factor.
    CONCLUSIONS: This study identified the essential genes and pathways associated with exercise and monocytes. Among these, four essential genes (TNF, DUSP1, CXCR4, and NR4A1) and the FoxO signaling pathway play vital roles in the immune function of monocytes. High-intensity exercise may improve the resistance of chronic inflammatory diseases by regulating the expression of these genes.
    Keywords:  biological pathways; chronic inflammation; differentially expressed genes; high-intensity exercise; monocytes
    DOI:  https://doi.org/10.3390/healthcare9060618
  6. Eur J Sport Sci. 2021 Jun 04. 1-22
      To examine the effects of a time-matched endurance versus concurrent training on circulating IL-6, IL-13, IL-15, IL-15Ra, FGF21 levels in postmenopausal women with obesity, and to determine these myokines response to endurance training pre- and postmenopause.
    Thirty-five sedentary postmenopausal women with obesity were randomly divided into endurance training (EN1, N=10), concurrent training (CON, N=13) or no training group (CT, N=12). Additionally, twelve sedentary premenopausal women with obesity were added to an endurance training group (EN2, N=12). Participants took part in a 12-week supervised intervention, performing 3 sessions/week of 60 min/session. Before and after the interventions, body composition and fitness were assessed, and blood samples obtained to measure serum myokines levels.
    Total fat mass decreased in all exercised groups (CON,-5.2%; EN1,-5.3%; EN2,-5.6%). In postmenopausal women, serum IL-6, IL-15 and IL-15Ra decreased after training (P<0.01), finding a pronounced reduction in IL-6 (-42% vs. -16%) and IL-15 (-50% vs. -31%) when comparing EN1 to CON (P<0.05). Serum FGF21 was only reduced in the EN1 (-27%; P=0.012). While EN1 and EN2 comparison, reported differences for IL-15Rα concentration (-28% vs. -40%; P=0.023). Finally, in EN2, the delta change of fat mass and IL-6, IL-15 and IL-15Rα were associated (r=0.605; r=0.546; r=0.515; P<0.05). IL-13 showed undetected concentrations.
    Circulating IL-6, IL-15 and FGF21 response to training is altered by exercise type but not by menopause in women with obesity. Endurance training promotes a higher reduction of these myokines, potentially activating their intricate immune and fat mass regulation roles in postmenopausal women with obesity.
    Keywords:  body composition; endurance and concurrent training; inflammation; menopause; myokines; physical activity
    DOI:  https://doi.org/10.1080/17461391.2021.1939430
  7. Aging (Albany NY). 2021 Jun 01. 13
      One of the genes which has been linked to the onset of juvenile/early onset Parkinson's disease (PD) is PINK1. There is evidence that supports the therapeutic potential of exercise in the alleviation of PD symptoms. It is possible that exercise may enhance synaptic plasticity, protect against neuro-inflammation and modulate L-Dopa regulated signalling pathways. We explored the effects of exercise on Pink1 deficient Drosophila melanogaster which undergo neurodegeneration and muscle degeneration. We used a 'power-tower' type exercise platform to deliver exercise activity to Pink1- and age matched wild-type Drosophila. Mitochondrial proteomic profiles responding to exercise were obtained. Of the 516 proteins identified, 105 proteins had different levels between Pink1- and wild-type non-exercised Drosophila. Gene ontology enrichment analysis and STRING network analysis highlighted proteins and pathways with altered expression within the mitochondrial proteome. Comparison of the Pink1- exercised proteome to wild-type proteomes showed that exercising the Pink1- Drosophila caused their proteomic profile to return towards wild-type levels.
    Keywords:  PINK1; drosophila; exercise; mitochondria; proteomics
    DOI:  https://doi.org/10.18632/aging.203128
  8. Int J Environ Res Public Health. 2021 May 17. pii: 5329. [Epub ahead of print]18(10):
      The coronavirus disease (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection, is leading to unknown and unusual health conditions that are challenging to manage. Post-COVID-19 syndrome is one of those challenges, having become increasingly common as the pandemic evolves. The latest estimates suggest that 10 to 20% of the SARS-CoV-2 patients who undergo an acute symptomatic phase are experiencing effects of the disease beyond 12 weeks after diagnosis. Although research is beginning to examine this new condition, there are still serious concerns about the diagnostic identification, which limits the best therapeutic approach. Exercise programs and physical activity levels are well-known modulators of the clinical manifestations and prognosis in many chronic diseases. This narrative review summarizes the up-to-date evidence on post-COVID-19 syndrome to contribute to a better knowledge of the disease and explains how regular exercise may improve many of these symptoms and could reduce the long-term effects of COVID-19.
    Keywords:  chronic COVID syndrome (CCS); functional capacity; long COVID; pneumonia; post-COVID-19 syndrome; post-acute sequelae of SARS-CoV-2 infection (PASC)
    DOI:  https://doi.org/10.3390/ijerph18105329
  9. Healthcare (Basel). 2021 May 27. pii: 637. [Epub ahead of print]9(6):
       OBJECTIVE: The purpose of this study was to evaluate the effects of a 4-week low-carbohydrate diet (LC) with or without exercise training on cardiometabolic health-related profiles in overweight/obese women.
    METHODS: Fifty overweight/obese Chinese women (age: 22.2 ± 3.3 years, body mass index (BMI): 25.1 ± 3.1 kg·m-2) were randomized to either a LC control group (LC-CON, n = 16), a LC and high-intensity interval training group (LC-HIIT, n = 17), or a LC and moderate-intensity continuous training group (LC-MICT, n = 17). All groups consumed LC for 4 weeks, while the LC-HIIT and LC-MICT groups followed an additional five sessions of HIIT (10 × 6 s cycling sprints and 9 s rest intervals, 2.5 min in total) or MICT (cycling continuously at 50-60% of peak oxygen uptake (VO2peak) for 30 min) weekly. Blood pressure, fasting glucose, insulin sensitivity, and several metabolic or appetite regulating hormones were measured before and after intervention.
    RESULTS: Significant reductions in body weight (- ~2.5 kg, p < 0.001, η2 = 0.772) and BMI (- ~1 unit, p < 0.001, η2 = 0.782) were found in all groups. Systolic blood pressure was reduced by 5-6 mmHg (p < 0.001, η2 = 0.370); fasting insulin, leptin, and ghrelin levels were also significantly decreased (p < 0.05), while insulin sensitivity was improved. However, there were no significant changes in fasting glucose, glucagon, and gastric inhibitory peptide levels. Furthermore, no group differences were found among the three groups, suggesting that extra training (i.e., LC-HIIT and LC-MICT) failed to trigger additional effects on these cardiometabolic profiles.
    CONCLUSIONS: The short-term carbohydrate restriction diet caused significant weight loss and improved blood pressure and insulin sensitivity in the overweight/obese women, although the combination with exercise training had no additional benefits on the examined cardiometabolic profiles. Moreover, the long-term safety and effectiveness of LC needs further study.
    Keywords:  appetite regulating hormones; cardiometabolic health; exercise; low-carbohydrate diet; obesity
    DOI:  https://doi.org/10.3390/healthcare9060637
  10. EBioMedicine. 2021 May 26. pii: S2352-3964(21)00190-0. [Epub ahead of print]68 103397
       BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative disease. ALS is determined by gene-environment interactions and improved understanding of these interactions may lead to effective personalised medicine. The role of physical exercise in the development of ALS is currently controversial.
    METHODS: First, we dissected the exercise-ALS relationship in a series of two-sample Mendelian randomisation (MR) experiments. Next we tested for enrichment of ALS genetic risk within exercise-associated transcriptome changes. Finally, we applied a validated physical activity questionnaire in a small cohort of genetically selected ALS patients.
    FINDINGS: We present MR evidence supporting a causal relationship between genetic liability to frequent and strenuous leisure-time exercise and ALS using a liberal instrument (multiplicative random effects IVW, p=0.01). Transcriptomic analysis revealed that genes with altered expression in response to acute exercise are enriched with known ALS risk genes (permutation test, p=0.013) including C9ORF72, and with ALS-associated rare variants of uncertain significance. Questionnaire evidence revealed that age of onset is inversely proportional to historical physical activity for C9ORF72-ALS (Cox proportional hazards model, Wald test p=0.007, likelihood ratio test p=0.01, concordance=74%) but not for non-C9ORF72-ALS. Variability in average physical activity was lower in C9ORF72-ALS compared to both non-C9ORF72-ALS (F-test, p=0.002) and neurologically normal controls (F-test, p=0.049) which is consistent with a homogeneous effect of physical activity in all C9ORF72-ALS patients.
    INTERPRETATION: Our MR approach suggests a positive causal relationship between ALS and physical exercise. Exercise is likely to cause motor neuron injury only in patients with a risk-genotype. Consistent with this we have shown that ALS risk genes are activated in response to exercise. In particular, we propose that G4C2-repeat expansion of C9ORF72 predisposes to exercise-induced ALS.
    FUNDING: We acknowledge support from the Wellcome Trust (JCK, 216596/Z/19/Z), NIHR (PJS, NF-SI-0617-10077; IS-BRC-1215-20017) and NIH (MPS, CEGS 5P50HG00773504, 1P50HL083800, 1R01HL101388, 1R01-HL122939, S10OD025212, P30DK116074, and UM1HG009442).
    Keywords:  Amyotrophic lateral sclerosis; C9ORF72; Mendelian randomisation; Physical exercise
    DOI:  https://doi.org/10.1016/j.ebiom.2021.103397
  11. Med Sci Sports Exerc. 2021 May 28.
       PURPOSE: This study investigated the effects of including sprints within low-intensity training (LIT)-sessions during a 14-d training camp focusing on LIT, followed by 10 days recovery (Rec), on performance and performance-related measures in elite cyclists.
    METHODS: During the camp, a sprint training group (SPR, n = 9) included 12x30-s maximal sprints during five LIT-sessions, whereas a control group (CON, n = 9) performed distance-matched LIT only. Training load was equally increased in both groups by 48 ± 27% during the training camp and subsequently decreased by -56 ± 23% during the recovery period compared to habitual training. Performance tests were conducted before the training camp (Pre) and after Rec. Muscle biopsies, haematological measures and stress/recovery questionnaires were collected Pre and after the camp (Post).
    RESULTS: 30-s sprint (SPR vs CON: 4 ± 4%, p < 0.01) and 5-min mean power (SPR vs CON: 4 ± 8%, p = 0.04) changed differently between groups. In muscle, Na+-K+β1 protein content changed differently between groups, decreasing in CON compared to SPR (-8 ± 14%, p = 0.04), while other proteins showed similar changes. SPR and CON displayed similar increases in red blood cell volume (SPR: 2.6 ± 4.7%, p = 0.07, CON: 3.9 ± 4.5%, p = 0.02) and VO2 at 4 mmol·L-1 [BLa-] (SPR: 2.5 ± 3.3%, p = 0.03, CON: 2.2 ± 3.0%, p = 0.04). No changes were seen for VO2max, Wmax, haematological measures, muscle enzyme activity and stress/recovery measures.
    CONCLUSION: Inclusion of 30-s sprints within LIT-sessions during a high-volume training camp affected competition-relevant performance-measures and Na+-K+β1 protein content differently than LIT only, without affecting sport-specific stress/recovery or any other physiological measure in elite cyclists.
    DOI:  https://doi.org/10.1249/MSS.0000000000002709