bims-exemet Biomed News
on Exercise metabolism
Issue of 2021‒02‒07
twenty-four papers selected by
Javier Botella Ruiz
Victoria University


  1. J Physiol. 2021 Feb;599(3): 769-770
    Powers SK, Hogan MC.
      
    Keywords:  exercise physiology; nutrition; skeletal muscle
    DOI:  https://doi.org/10.1113/JP281003
  2. Front Nutr. 2020 ;7 628405
    Roberson PA, Mobley CB, Romero MA, Haun CT, Osburn SC, Mumford PW, Vann CG, Greer RA, Ferrando AA, Roberts MD.
      Introduction: Amino acid transporters are essential for cellular amino acid transport and promoting protein synthesis. While previous literature has demonstrated the association of amino acid transporters and protein synthesis following acute resistance exercise and amino acid supplementation, the chronic effect of resistance exercise and supplementation on amino acid transporters is unknown. The purpose herein was to determine if amino acid transporters and amino acid metabolic enzymes were related to skeletal muscle hypertrophy following resistance exercise training with different nutritional supplementation strategies. Methods: 43 college-aged males were separated into a maltodextrin placebo (PLA, n = 12), leucine (LEU, n = 14), or whey protein concentrate (WPC, n = 17) group and underwent 12 weeks of total-body resistance exercise training. Each group's supplement was standardized for total energy and fat, and LEU and WPC supplements were standardized for total leucine (6 g/d). Skeletal muscle biopsies were obtained prior to training and ~72 h following each subject's last training session. Results: All groups increased type I and II fiber cross-sectional area (fCSA) following training (p < 0.050). LAT1 protein increased following training (p < 0.001) and increased more in PLA than LEU and WPC (p < 0.050). BCKDHα protein increased and ATF4 protein decreased following training (p < 0.001). Immunohistochemistry indicated total LAT1/fiber, but not membrane LAT1/fiber, increased with training (p = 0.003). Utilizing all groups, the change in ATF4 protein, but no other marker, trended to correlate with the change in fCSA (r = 0.314; p = 0.055); however, when regression analysis was used to delineate groups, the change in ATF4 protein best predicted the change in fCSA only in LEU (r 2 = 0.322; p = 0.043). In C2C12 myoblasts, LAT1 protein overexpression caused a paradoxical decrease in protein synthesis levels (p = 0.002) and decrease in BCKDHα protein (p = 0.001). Conclusions: Amino acid transporters and metabolic enzymes are affected by resistance exercise training, but do not appear to dictate muscle fiber hypertrophy. In fact, overexpression of LAT1 in vitro decreased protein synthesis.
    Keywords:  ATF4; BCKDH; amino acid metabolism; protein supplementation; protein synthesis
    DOI:  https://doi.org/10.3389/fnut.2020.628405
  3. Int J Mol Sci. 2021 Feb 03. pii: 1539. [Epub ahead of print]22(4):
    De Sanctis P, Filardo G, Abruzzo PM, Astolfi A, Bolotta A, Indio V, Di Martino A, Hofer C, Kern H, Löfler S, Marcacci M, Marini M, Zampieri S, Zucchini C.
      In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared-the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.
    Keywords:  aging; exercise training; gene expression; non-coding RNAs; skeletal muscle
    DOI:  https://doi.org/10.3390/ijms22041539
  4. Sci Adv. 2021 Jan;pii: eabd9502. [Epub ahead of print]7(4):
    Chen Z, Li B, Zhan RZ, Rao L, Bursac N.
      Chronic inflammatory diseases often lead to muscle wasting and contractile deficit. While exercise can have anti-inflammatory effects, the underlying mechanisms remain unclear. Here, we used an in vitro tissue-engineered model of human skeletal muscle ("myobundle") to study effects of exercise-mimetic electrical stimulation (E-stim) on interferon-γ (IFN-γ)-induced muscle weakness. Chronic IFN-γ treatment of myobundles derived from multiple donors induced myofiber atrophy and contractile loss. E-stim altered the myobundle secretome, induced myofiber hypertrophy, and attenuated the IFN-γ-induced myobundle wasting and weakness, in part by down-regulating JAK (Janus kinase)/STAT1 (signal transducer and activator of transcription 1) signaling pathway amplified by IFN-γ. JAK/STAT inhibitors fully prevented IFN-γ-induced myopathy, confirming the critical roles of STAT1 activation in proinflammatory action of IFN-γ. Our results reveal a previously unknown mechanism of the cell-autonomous anti-inflammatory effects of muscle exercise and establish the utility of human myobundle platform for studies of inflammatory muscle disease and therapy.
    DOI:  https://doi.org/10.1126/sciadv.abd9502
  5. Sci Rep. 2021 Feb 02. 11(1): 2836
    Reljic D, Frenk F, Herrmann HJ, Neurath MF, Zopf Y.
      Physical activity is a cornerstone in the treatment of obesity and metabolic syndrome (MetS). Given the leading physical activity barrier of time commitment and safety concerns about vigorous exercise in high-risk groups, this study aimed to investigate the effects of two extremely time-efficient training protocols (< 30 min time effort per week), either performed as high- (HIIT) or moderate-intensity interval training (MIIT) over 12 weeks, in obese MetS patients. In total, 117 patients (49.8 ± 13.6 years, BMI: 38.2 ± 6.2 kg/m2) were randomized to HIIT (n = 40), MIIT (n = 37) or an inactive control group (n = 40). All groups received nutritional counseling to support weight loss. Maximal oxygen uptake (VO2max), MetS severity (MetS z-score), body composition and quality of life (QoL) were assessed pre-and post-intervention. All groups significantly reduced body weight (~ 3%) but only the exercise groups improved VO2max, MetS z-score and QoL. VO2max (HIIT: + 3.1 mL/kg/min, p < 0.001; MIIT: + 1.2 mL/kg/min, p < 0.05) and MetS z-score (HIIT: - 1.8 units, p < 0.001; MIIT: - 1.2 units, p < 0.01) improved in an exercise intensity-dependent manner. In conclusion, extremely low-volume interval training, even when done at moderate intensity, is sufficiently effective to improve cardiometabolic health in obese MetS patients. These findings underpin the crucial role of exercise in the treatment of obesity and MetS.
    DOI:  https://doi.org/10.1038/s41598-021-82372-4
  6. Physiol Rep. 2021 Feb;9(3): e14497
    Kwak SE, Bae JH, Lee JH, Shin HE, Zhang D, Cho SC, Song W.
      Recent studies have shown that exercise improves skeletal muscle and cognitive function by stimulating the secretion of numerous molecules. In particular, previous studies have suggested that exercise-induced beta-hydroxybutyrate (BHB) release might improve skeletal muscle and cognitive function, but to date these studies have been limited to cell and animal models. Therefore, we aimed to determine how an exercise-induced increase in BHB affects skeletal muscle and cognitive function at a cellular level, in an animal model, and in humans. The effects of BHB on skeletal muscle and cognitive function were determined by treating C2C12 and C6 cell lines with BHB, and by measuring the skeletal muscle and serum BHB concentrations in aged mice after endurance or resistance exercise. In addition, serum BHB concentration was measured before and after high-speed band exercise in elderly people, and its relationships with muscle and cognitive function were analyzed. We found that BHB increased cell viability and brain-derived neurotrophic factor expression level in C6 cells, and endurance exercise, but not resistance exercise, increased the muscle BHB concentration in aged mice. Furthermore, the BHB concentration was positively related to skeletal muscle and cognitive function. Exercise did not increase the serum BHB concentration in the elderly people and BHB did not correlate with cognitive function, but after excluding the five people with the highest preexisting serum concentrations of BHB, the BHB concentrations of the remaining participants were increased by exercise, and the concentration showed a tendency toward a positive correlation with cognitive function. Thus, the BHB released by skeletal muscle following endurance exercise may improve muscle and cognitive function in animals and humans.
    Keywords:  beta-hydroxybutyrate; cognitive function; exercise; skeletal muscle
    DOI:  https://doi.org/10.14814/phy2.14497
  7. J Diabetes Metab Disord. 2020 Dec;19(2): 1003-1009
    E Silva AS, Lacerda FV, da Mota MPG.
      Elevated plasma homocysteine concentration is a risk factor for cardiovascular disease, which seems to be the main cause of increased mortality in patients with type 2 diabetes. Previous studies have demonstrated the effect of exercise on homocysteine levels and the magnitude of these benefits seems to depend on the type, mode and frequency of training. The present study aimed to compare the effects of aerobic and resistance training on plasma homocysteine in individuals with type 2 diabetes. The study included 15 individuals undergoing aerobic training, 14 subjects undergoing resistance training, and 18 individuals in the control group. Homocysteine, total cholesterol and fractions, glucose, and anthropometric measurements were conducted. The training program lasted 16 weeks. Aerobic training was performed twice a week and lasted 75 min, and resistance training was performed twice a week and lasted 75 min. Homocysteine levels were not significantly different between before and after training. High-density lipoprotein levels increased in both training groups and decreased in the control group. Glucose levels decreased after aerobic and resistance training. Body fat mass (percentage and total) decreased in both training group, but with more expression in the aerobic group. We conclude that 16-week aerobic and resistance training programs did not significantly affect plasma homocysteine levels in patients with type 2 diabetes. Nevertheless, these training programs yielded positive results in HDL control, plasma glucose, and body composition.
    Keywords:  Aerobic training; Atherosclerosis; Diabetes; Homocysteine; Resistance training
    DOI:  https://doi.org/10.1007/s40200-020-00596-z
  8. Thorax. 2021 Feb 04. pii: thoraxjnl-2020-215135. [Epub ahead of print]
    Marillier M, Bernard AC, Verges S, Moran-Mendoza O, O'Donnell DE, Neder JA.
      BACKGROUND: Exercise-induced hypoxaemia is a hallmark of chronic fibrotic interstitial lung disease (f-ILD). It remains unclear whether patients' severe hypoxaemia may exaggerate locomotor muscle fatigue and, if so, to what extent oxygen (O2) supplementation can ameliorate these abnormalities.METHODS: Fifteen patients (12 males, 9 with idiopathic pulmonary fibrosis) performed a constant-load (60% peak work rate) cycle test to symptom limitation (Tlim) while breathing medical air. Fifteen age-matched and sex-matched controls cycled up to patients' Tlim. Patients repeated the exercise test on supplemental O2 (42%±7%) for the same duration. Near-infrared spectroscopy assessed vastus lateralis oxyhaemoglobin concentration ((HbO2)). Pre-exercise to postexercise variation in twitch force (∆Tw) induced by femoral nerve magnetic stimulation quantified muscle fatigue.
    RESULTS: Patients showed severe hypoxaemia (lowest O2 saturation by pulse oximetry=80.0%±7.6%) which was associated with a blunted increase in muscle (HbO2) during exercise vs controls (+1.3±0.3 µmol vs +4.4±0.4 µmol, respectively; p<0.001). Despite exercising at work rates ∼ one-third lower than controls (42±13 W vs 66±13 W), ∆Tw was greater in patients (∆Tw/external work performed by the leg muscles=-0.59±0.21 %/kJ vs -0.25±0.19 %/kJ; p<0.001). Reversal of exertional hypoxaemia with supplemental O2 was associated with a significant increase in muscle (HbO2), leading to a reduced decrease in ∆Tw in patients (-0.33±0.19 %/kJ; p<0.001 vs air). Supplemental O2 significantly improved leg discomfort (p=0.005).
    CONCLUSION: O2 supplementation during exercise improves leg muscle oxygenation and fatigue in f-ILD. Lessening peripheral muscle fatigue to enhance exercise tolerance is a neglected therapeutic target that deserves clinical attention in this patient population.
    Keywords:  Long Term Oxygen Therapy (LTOT); exercise; interstitial fibrosis; lung physiology; pulmonary rehabilitation; respiratory measurement; short burst oxygen therapy
    DOI:  https://doi.org/10.1136/thoraxjnl-2020-215135
  9. Front Physiol. 2020 ;11 583155
    Kim YS, van der Ster BJP, Brassard P, Secher NH, van Lieshout JJ.
      The human brain is constantly active and even small limitations to cerebral blood flow (CBF) may be critical for preserving oxygen and substrate supply, e.g., during exercise and hypoxia. Exhaustive exercise evokes a competition for the supply of oxygenated blood between the brain and the working muscles, and inability to increase cardiac output sufficiently during exercise may jeopardize cerebral perfusion of relevance for diabetic patients. The challenge in diabetes care is to optimize metabolic control to slow progression of vascular disease, but likely because of a limited ability to increase cardiac output, these patients perceive aerobic exercise to be more strenuous than healthy subjects and that limits the possibility to apply physical activity as a preventive lifestyle intervention. In this review, we consider the effects of functional activation by exercise on the brain and how it contributes to understanding the control of CBF with the limited exercise tolerance experienced by type 2 diabetic patients. Whether a decline in cerebral oxygenation and thereby reduced neural drive to working muscles plays a role for "central" fatigue during exhaustive exercise is addressed in relation to brain's attenuated vascular response to exercise in type 2 diabetic subjects.
    Keywords:  cardiac output; cerebral blood flow; cerebral metabolism; cerebral oxygenation; diabetes; vascular conductance
    DOI:  https://doi.org/10.3389/fphys.2020.583155
  10. J Obes Metab Syndr. 2021 Feb 01.
    Lee JH, Zhang D, Kwak SE, Shin HE, Song W.
      Background: Exercise and high fat, high sucrose restriction diets are well known treatments for obesity. The aim of this study was to measure the effects of those lifestyle interventions on molecular transducers of exercise, such as Nr4a3, mitochondria-associated proteins, and muscle function.Methods: We conducted 8 weeks of treadmill exercise and sucrose or fat restriction diets in obese mice. The mice were divided into eight groups: the normal diet (CON) group, normal diet with exercise (CONEX) group, high fat, high sucrose diet (HFHS) group, HFHS with exercise (HFHSEX) group, sucrose restriction (SR) group, SR with exercise (SREX) group, high fat, high sucrose restriction group (ND) group, and ND with exercise (NDEX) group.
    Results: The 8 weeks of exercise reduced body weight, improved lipid profiles (total cholesterol, triglycerides), and increased hanging time. The combination of exercise and a fat and sucrose restriction diet improved glucose tolerance and increased grip strength. The 8 weeks of intervention did not significantly affect the Nr4a3 protein level. The sucrose and fat restriction diet increased the pAKT/AKT ratio, and its level was lower in the HFHS group. Exercise increased the protein expression level of PGC1alpha in obese conditions. Moreover, SR led reduced the pAMPK/AMPK ratio and PGC1alpha to the control level.
    Conclusion: The 8 weeks of exercise or a sucrose and fat restriction diet improved metabolic indicators and muscle function. SR reduced pAMPK/AMPK and PGC1alpha to the control level. Nr4a3 protein expression was not significantly changed by either exercise or a fat and sucrose restriction diet.
    Keywords:  Exercise; Fat; Metabolic diseases; Mitochondria; Nr4a3; Obesity; Sucrose
    DOI:  https://doi.org/10.7570/jomes20043
  11. Phys Act Nutr. 2020 Dec;24(4): 15-23
    Cho HS, Lee WS, Yoon KJ, Park SH, Shin HE, Kim YS, Chang H, Moon HY.
      Purpose: Lactate is a principal energy substrate for the brain during exercise. A single bout of high-intensity interval exercise (HIIE) can increase the blood lactate level, brain lactate uptake, and executive function (EF). However, repeated HIIE can attenuate exercise-induced increases in lactate level and EF. The lactate levels in the brain and blood are reported to be correlated with exercise-enhanced EF. However, research is yet to explain the cause-and-effect relationship between lactate and EF. This study examined whether lactate consumption improves the attenuated exerciseenhanced EF caused by repeated HIIE.Methods: Eleven healthy men performed two sets of HIIE, and after each set, 30 min were given for rest and examination. In the 2nd set, the subjects consumed experimental beverages containing (n = 6) and not containing (n = 5) lactate. Blood, cardiovascular, and psychological variables were measured, and EF was evaluated by the computerized color-word Stroop test.
    Results: The lactate group had a higher EF (P < 0.05) and tended to have a higher blood lactate level (P = 0.082) than the control group in the 2nd set of HIIE. Moreover, blood lactate concentration was correlated with the interference score (i.e., reverse score of EF) (r = -0.394; P < 0.05).
    Conclusion: Our results suggest that the attenuated exercise-enhanced EF after repeated HIIE can be improved through lactate consumption. However, the role of lactate needs to be elucidated in future studies, as it can be used for improving athletes' performance and also in cognitive decline-related clinical studies.
    Keywords:  Brain energy; Cognitive function; Exercise; Fatigue; Performance; Sports drink
    DOI:  https://doi.org/10.20463/pan.2020.0023
  12. Phys Act Nutr. 2020 Dec;24(4): 28-33
    Lim IS.
      Purpose: This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplement on delayed onset muscle soreness (DOMS) by analyzing the maximum muscle strength and indicators of muscle damage.Methods: Twelve men with majors in physical education were assigned to the BCAA group and placebo group in a double-blinded design, and repeated measurements were conducted. DOMS was induced with an isokinetic exercise. Following BCAA administration, the changes in the knee extension peak torque, flexion peak torque, aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) concentrations were analyzed. The maximum knee muscle strength was measured at the baseline (pre-D0) following BCAA administration for 5 days before exercise (-D5, -4D, -3D, -2D, -1D). In contrast, the post-treatment measurements (D3) were recorded after BCAA administration for 3 days (post-D0, D1, D2). Blood samples were obtained before (pre-D0), immediately after (post-D0), 24 h (D1), 48 h (D2), and 72 h (D3) after the exercise to analyze the indicators of muscle strength. BCAA was administered twice daily for 8 days (5 days and 3 days before inducing DOMS and during the experimental period, respectively).
    Results: There was no difference in the flexion peak torque between the groups. However, the BCAA group showed a significantly higher extension peak torque at D3 (second isokinetic exercise), compared to the placebo group (p<.05). There was no difference in AST changes between the groups. Nonetheless, the CK and LDH were significantly reduced in the BCAA group, compared to the placebo group. There was no correlation between the extension peak torque and flexion peak torque. However, the CK and LDH increased proportionately in DOMS. Moreover, their concentrations significantly increased with a decreasing peak torque (p<.01).
    Conclusion: An exercise-induced DOMS results in a decrease in the peak torque and a proportional increase in the CK and LDH concentrations. Moreover, the administration of BCAA inhibits the reduction of the extension peak torque and elevation of CK and LDH concentrations. Therefore, BCAA might be administered as a supplement to maintain the muscle strength and prevent muscle damage during vigorous exercises that may induce DOMS in sports settings.
    Keywords:  AST; BCAA; CK; DOMS; LDH; indicators of muscle damage; knee peak torque
    DOI:  https://doi.org/10.20463/pan.2020.0025
  13. J Gerontol A Biol Sci Med Sci. 2021 Feb 04. pii: glab040. [Epub ahead of print]
    Reitelseder S, Bülow J, Holm L.
      Older adults' skeletal muscle has shown to be less responsive to anabolic stimuli as compared to young both in vitro, in short and controlled in vivo settings and in long-term training studies. However, to translate controlled mechanistic findings to long-term adaptations intermediate measures allowing daily life routines with regard to activity and diet would be useful to evaluate physiological interventions. The purpose of this study was to investigate the exercise effect in young and older adults with two independent methods to measure muscle protein synthesis rate. Healthy young and old men were recruited to the study protocol where myofibrillar fractional synthesis rate (FSR) was measured during 2 d allowing normal activities of daily living (ADL) with D2O labeled alanine and during 4 h in the overnight fasted state with [ 13C6]phenylalanine infusion. During this period one leg completed an exercise session every day (exercise leg) while the contralateral leg was kept inactive (normal leg). Both legs were used for ADL. 2-d myofibrillar FSR was significantly higher in the exercise leg in both young and old as compared to normal leg with no age difference. The 4-h overnight fasted myofibrillar FSR showed that only young exercise leg was significantly higher than normal leg. The present findings support the notion that anabolic resistance exists in the skeletal muscle of healthy older men when evaluated in controlled settings. However, this response is not as clear when measured during daily life where variance is greater, which calls for further investigations in larger cohorts.
    Keywords:  Alanine; Daily living; Deuterated water; Muscle protein synthesis; Phenylalanine
    DOI:  https://doi.org/10.1093/gerona/glab040
  14. Sports Med. 2021 Feb 02.
    Li Z, McKenna ZJ, Kuennen MR, Magalhães FC, Mermier CM, Amorim FT.
      Exertional heat stroke (EHS) is a life-threatening condition that affects mainly athletes, military personnel, firefighters, and occupational workers. EHS is frequently observed in non-compensable conditions (where the body is unable to maintain a steady thermal balance) as a result of heavy heat stress and muscle contraction associated with prolonged and strenuous physical and occupational activities, resulting in central nervous system dysfunction followed by multi-organ damage and failure. Since the pathophysiology of EHS is complex and involves multiple organs and systems, any condition that changes the interrelated systems may increase the risk for EHS. It has been suggested that exercise-induced muscle damage (EIMD) can lead to thermoregulatory impairment and systemic inflammation, which could be a potential predisposing factor for EHS. In this review article, we aim to (1) address the evidence of EIMD as a predisposing factor for EHS and (2) propose a possible mechanism of how performing muscle-damaging exercise in the heat may aggravate muscle damage and subsequent risk of EHS and acute kidney injury (AKI). Such an understanding could be meaningful to minimize the risks of EHS and AKI for individuals with muscle damage due to engaging in physical work in hot environments.
    DOI:  https://doi.org/10.1007/s40279-021-01427-8
  15. Int J Environ Res Public Health. 2021 Feb 01. pii: 1285. [Epub ahead of print]18(3):
    Cirer-Sastre R, Corbi F, López-Laval I, Carranza-García LE, Reverter-Masià J.
      To examine the exercise-induced release of cardiac troponin T (cTnT) in adolescent and adult swimmers. Thirty-two trained male (18 adolescents, 14 adults) swam at maximal pace in a 45 min distance trial, and blood samples were drawn before, immediately and 3 h after exercise for subsequent cTnT analysis and comparison. Having comparable training experience and baseline values of cTnT (p = 0.78 and p = 0.13), adults exercised at lower absolute and relative intensity (p < 0.001 and p < 0.001, respectively), but presented higher immediate cTnT after exercise than adolescents (p < 0.001). Despite that, peak concentrations were observed at 3 h post exercise and peak elevations were comparable between groups (p = 0.074). Fourteen (44%) apparently healthy subjects exceeded the cutoff value for myocardial infarction (MI). Adolescents presented a delayed elevation of cTnT compared with adults, but achieved similar peak values.
    Keywords:  biomarkers; growth; heart damage; swimming
    DOI:  https://doi.org/10.3390/ijerph18031285
  16. Am J Physiol Regul Integr Comp Physiol. 2021 Feb 03.
    Matsui T.
      Brain glycogen localized in astrocytes produces lactate via cAMP signaling, which regulates memory functions and endurance capacity. Exhaustive endurance exercise with hypoglycemia decreases brain glycogen, although the mechanism underlying this phenomenon remains unclear. Since insulin-induced hypoglycemia decreases brain glycogen, this study tested the hypothesis that hypoglycemia mediates exercise-induced brain glycogen decrease. To test the hypothesis, the effects of insulin- and exhaustive exercise-induced hypoglycemia on brain glycogen levels were compared using the microwave irradiation method in adult Wistar rats. The insulin challenge and exhaustive exercise induced similar levels of severe hypoglycemia. Glycogen in the hypothalamus and cerebellum decreased similarly with the insulin challenge and exhaustive exercise; however, glycogen in the cortex, hippocampus, and brainstem of the exercise group were lower compared to the insulin group. Blood glucose correlated positively with brain glycogen, but the slope of regression lines was greater in the exercise group compared to the insulin group in the cortex, hippocampus, and brainstem, but not the hypothalamus and cerebellum. Brain lactate and cAMP levels in the hypothalamus and cerebellum increased similarly with the insulin challenge and exhaustive exercise, but those in the cortex, hippocampus, and brainstem of the exercise group were higher compared to the insulin group. These findings support the hypothesis that hypoglycemia mediates the exercise-induced reduction in brain glycogen, at least in the hypothalamus and cerebellum. However, glycogen reduction during exhaustive endurance exercise in the cortex, hippocampus, and brainstem is not due to hypoglycemia alone, implicating the role of exercise-specific neuronal activity in brain glycogen decrease.
    Keywords:  Brain energetics; Cortex; Hippocampus; Skeletal muscle; cAMP
    DOI:  https://doi.org/10.1152/ajpregu.00119.2020
  17. Int J Mol Sci. 2021 Jan 26. pii: 1208. [Epub ahead of print]22(3):
    Makhnovskii PA, Bokov RO, Kolpakov FA, Popov DV.
      Inactivity is associated with the development of numerous disorders. Regular aerobic exercise is broadly used as a key intervention to prevent and treat these pathological conditions. In our meta-analysis we aimed to identify and compare (i) the transcriptomic signatures related to disuse, regular and acute aerobic exercise in human skeletal muscle and (ii) the biological effects and transcription factors associated with these transcriptomic changes. A standardized workflow with robust cut-off criteria was used to analyze 27 transcriptomic datasets for the vastus lateralis muscle of healthy humans subjected to disuse, regular and acute aerobic exercise. We evaluated the role of transcriptional regulation in the phenotypic changes described in the literature. The responses to chronic interventions (disuse and regular training) partially correspond to the phenotypic effects. Acute exercise induces changes that are mainly related to the regulation of gene expression, including a strong enrichment of several transcription factors (most of which are related to the ATF/CREB/AP-1 superfamily) and a massive increase in the expression levels of genes encoding transcription factors and co-activators. Overall, the adaptation strategies of skeletal muscle to decreased and increased levels of physical activity differ in direction and demonstrate qualitative differences that are closely associated with the activation of different sets of transcription factors.
    Keywords:  disuse; exercise; extracellular matrix; heterodimer; mitochondrion; skeletal muscle; transcription factors; transcriptome
    DOI:  https://doi.org/10.3390/ijms22031208
  18. J Diabetes Metab Disord. 2020 Dec;19(2): 669-674
    Arefirad T, Shakeri N, Ebrahim K, Nasli-Esfahani E.
      Purpose: The purpose of this study was to investigate the effects of interval training on cardio metabolic risk factors and nitric oxide in type 2 diabetes patients.Method: This single blinded randomized controlled trial was conducted at cardiology clinic of Rajaee hospital in Karaj. Thirty female patients with type 2 diabetes randomly assigned to interval training exercise (n = 15) and control (n = 15). In interval training exercise patients received interval training exercise with 18 sessions (three sessions per week). Each training session took 25 min and consists a single set of exercise with 10 time repetitions. Training was performed on a cycle ergometer set in constant watt mode at a pedal cadence of 80-100 revolutions/min. Each repetition of the training takes 60 s and there will be a 60 s recovery pried between each repetition. Each training session include a 3-min warm-up and 2-min cool-down at 50 W for a total of 25 min. Blood samples and of all the subjects were taken at baseline, 3 weeks after intervention and at the end of the study (6 weeks).
    Results: In intervention group, comparing with controls participants, a significant decrease were observed in levels of total cholesterol, triglyceride and HA1c after training program (p < 0.05). Moreover,exercise significantly increased the level of NOx (p < 0.05). Other cardiometabolic risk factors including SBP, DBP, FPG, LDL, HDL, insulin level, insulin resistance, HR, VO2 max, did not show significant differences between the two groups (p > 0.05).
    Conclusion: Results of current study showed that interval training as a type of planned physical activity can be effective in lowering cardiovascular risk factors, especially lowering cholesterol and triglycerides, and can also have a beneficial effect on improving NO.
    Keywords:  CMRFs; Cardio metabolic risk factors; Diabetes mellitus type 2; Insulin resistance; Interval training; Nitric oxide
    DOI:  https://doi.org/10.1007/s40200-019-00486-z
  19. J Diabetes Metab Disord. 2020 Dec;19(2): 1089-1096
    Sabzevari Rad R, Shirvani H, Mahmoodzadeh Hosseini H, Shamsoddini A, Samadi M.
      Purpose: This study aims to investigate the effect of high-intensity interval training (HIIT) on gene expression of MicroRNA-126 (miR-126) and serum concentration of vascular endothelial growth factor/ sprouty related EVH1 domain containing 1/ rapidly accelerated fibrosarcoma 1 (VEGF/Spred-1/Raf-1) proteins effective in cardiac tissue angiogenesis of diabetic rats.Methods: Forty male Wistar rats were randomly divided into four groups of healthy control (HC), diabetic control (DC), diabetic with HIIT training (DT), and healthy with HIIT training (HT). HIIT was performed 6 days per week for 6 weeks (with the overload). Diabetes was induced via the combination of intraperitoneal injection of streptozotocin and high-fat foods.
    Results: Diabetes remarkably diminished the expressions of miR-126, VEGF and Raf-1 proteins, and augmented Spred-1 expression. Meanwhile, the implementation of HIIT gave rise to a significant enhancement in expression of miR-126 heart tissue (P < 0.01), and subsequently increased the expression of VEGF and Raf-1 proteins (P < 0.01), and declined Spred-1 expression (P < 0.01) in the training group compared to the control group.
    Conclusion: The results of this study show that HIIT increases the expression of miR-126 by activating the angiogenesis pathway of the heart tissue. Increased angiogenesis through the miR-126 pathway is vital to compensate for heart destruction induced by diabetes. Thus, the use of standard interval exercise can be introduced as a novel therapeutic target for diabetic cardiomyopathy.
    Keywords:  Diabetes mellitus; Exercise; Heart muscle; VEGF; miR-126
    DOI:  https://doi.org/10.1007/s40200-020-00610-4
  20. Front Physiol. 2020 ;11 621226
    Gharahdaghi N, Phillips BE, Szewczyk NJ, Smith K, Wilkinson DJ, Atherton PJ.
      Maintenance of skeletal muscle mass throughout the life course is key for the regulation of health, with physical activity a critical component of this, in part, due to its influence upon key hormones such as testosterone, estrogen, growth hormone (GH), and insulin-like growth factor (IGF). Despite the importance of these hormones for the regulation of skeletal muscle mass in response to different types of exercise, their interaction with the processes controlling muscle mass remain unclear. This review presents evidence on the importance of these hormones in the regulation of skeletal muscle mass and their responses, and involvement in muscle adaptation to resistance exercise. Highlighting the key role testosterone plays as a primary anabolic hormone in muscle adaptation following exercise training, through its interaction with anabolic signaling pathways and other hormones via the androgen receptor (AR), this review also describes the potential importance of fluctuations in other hormones such as GH and IGF-1 in concert with dietary amino acid availability; and the role of estrogen, under the influence of the menstrual cycle and menopause, being especially important in adaptive exercise responses in women. Finally, the downstream mechanisms by which these hormones impact regulation of muscle protein turnover (synthesis and breakdown), and thus muscle mass are discussed. Advances in our understanding of hormones that impact protein turnover throughout life offers great relevance, not just for athletes, but also for the general and clinical populations alike.
    Keywords:  hormone; hypertrophy; muscle growth; protein synthesis; resistance exercise
    DOI:  https://doi.org/10.3389/fphys.2020.621226
  21. Physiol Rep. 2021 Feb;9(3): e14730
    McBean SE, Church JE, Thompson BK, Taylor CJ, Fitton JH, Stringer DN, Karpiniec SS, Park AY, van der Poel C.
      Fucoidan is a sulfated polysaccharide found in a range of brown algae species. Growing evidence supports the long-term supplementation of fucoidan as an ergogenic aid to improve skeletal muscle performance. The aim of this study was to investigate the effect of fucoidan on the skeletal muscle of mice. Male BL/6 mice (N = 8-10) were administered a novel fucoidan blend (FUC, 400 mg/kg/day) or vehicle (CON) for 4 weeks. Treatment and control experimental groups were further separated into exercise (CON+EX, FUC+EX) or no-exercise (CON, FUC) groups, where exercised groups performed 30 min of treadmill training three times per week. At the completion of the 4-week treatment period, there was a significant increase in cross-sectional area (CSA) of muscle fibers in fucoidan-treated extensor digitorum longus (EDL) and soleus fibers, which was accompanied by a significant increase in tibialis anterior (TA) muscle force production in fucoidan-treated groups. There were no significant changes in grip strength or treadmill time to fatigue, nor was there an effect of fucoidan or exercise on mass of TA, EDL, or soleus muscles. In gastrocnemius muscles, there was no change in mRNA expression of mitochondrial biogenesis markers PGC-1α and Nrf-2 in any experimental groups; however, there was a significant effect of fucoidan supplementation on myosin heavy chain (MHC)-2x, but not MHC-2a, mRNA expression. Overall, fucoidan increased muscle size and strength after 4 weeks of supplementation in both exercised and no-exercised mice suggesting an important influence of fucoidan on skeletal muscle physiology.
    Keywords:  Fucoidan; endurance exercise; muscle contraction; muscle fatigue; skeletal muscle
    DOI:  https://doi.org/10.14814/phy2.14730
  22. J Diabetes Metab Disord. 2020 Dec;19(2): 717-726
    Soltani N, Marandi SM, Kazemi M, Esmaeil N.
      Objective: The effects of exercise training on suppression of inflammation have been proposed as a therapeutic approach in recent years to modify the obesity-induced inflammatory status and immunometabolic disorders. The present study aimed to assess the impacts of an all-extremity combined high-intensity interval training (HIIT) on inflammatory state and glycolipid metabolism in young sedentary overweight and obese females.Method: This was an quasi-experimental study which was applied by comparing two groups. The participants were allocated to two active (AG, n = 15) and inactive (IG, n = 15) groups. The serum level of adiponectin, interleukin (IL)-10, pentraxin 3 (PTX3), and tumor-necrosis factor α (TNFα) was measured in all subjects. Also, glycolipid metabolism was assessed by measuring the fasting lipid profile parameters, glucose, and insulin levels and calculating the homeostasis model assessment of insulin resistance (HOMA2-IR).
    Results: Following a 10-week combined all-extremity HIIT in the active subjects, the TNFα, PTX3/IL-10, and TNFα/adiponectin were significantly reduced. However, the absolute levels of adiponectin, IL-10, and PTX3 remained unchanged. Additionally, a significant decrease was found in insulin, LDL, and HOMA2-IR, while insulin sensitivity and HDL levels showed a significant increase in the active group compared to the inactive group.
    Conclusions: Our 10-week time-efficient combined all-extremity HIIT promoted an anti-inflammatory state and glycolipid metabolism improvement, suggesting this protocol as a practical therapeutic approach in sedentary obese females.
    Keywords:  Combined training; Exercise therapy; Meta-inflammation; Obesity; PTX3
    DOI:  https://doi.org/10.1007/s40200-020-00550-z