Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men

Purpose We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men. Methods Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively. Results Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604). Conclusion There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men.

Methylglyoxal reduces molecular responsiveness to 4 weeks of endurance exercise in mouse plantaris muscle

Endurance exercise triggers skeletal muscle adaptations, including enhanced insulin signaling, glucose metabolism, and mitochondrial biogenesis. However, exercise-induced skeletal muscle adaptations may not occur in some cases, a condition known as exercise-resistance. Methylglyoxal (MG) is a highly reactive dicarbonyl metabolite and has detrimental effects on the body such as causing diabetic complications, mitochondrial dysfunction, and inflammation. This study aimed to clarify the effect of methylglyoxal on skeletal muscle molecular adaptations following endurance exercise. Mice were randomly divided into 4 groups (n = 12 per group): sedentary control group, voluntary exercise group, MG-treated group, and MG-treated with voluntary exercise group. Mice in the voluntary exercise group were housed in a cage with a running wheel, while mice in the MG-treated groups received drinking water containing 1% MG. Four weeks of voluntary exercise induced several molecular adaptations in the plantaris muscle, including increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), mitochondria complex proteins, toll-like receptor 4 (TLR4), 72-kDa heat shock protein (HSP72), hexokinase II, and glyoxalase 1; this also enhanced insulin-stimulated Akt Ser473 phosphorylation and citrate synthase activity. However, these adaptations were suppressed with MG treatment. In the soleus muscle, the exercise-induced increases in the expression of TLR4, HSP72, and advanced glycation end products receptor 1 were inhibited with MG treatment. These findings suggest that MG is a factor that inhibits endurance exercise-induced molecular responses including mitochondrial adaptations, insulin signaling activation, and the upregulation of several proteins related to mitochondrial biogenesis, glucose handling, and glycation in primarily fast-twitch skeletal muscle.

Effect of Moderate-Intensity Endurance Exercise on Inflammatory Cytokines in Leukocytes of Dogs

This study aimed to investigate the effect of a treadmill exercise on hematological and serum biochemical parameters and the expression of immune-related cytokine genes in leukocytes. For the experiment, six healthy adult dogs were divided into exercise and control groups. The exercise group performed an endurance exercise three times a week for four weeks. Blood samples were collected before exercise, two weeks after exercise, and post-exercise, and hematological and serum biochemical analysis and cytokine gene analysis were conducted. In the exercise group, white blood cell count (WBC), aspartate aminotransferase, serum alkaline phosphatase, and glucose levels were significantly decreased, but there was no change in the control group. The mRNA expression of TNF-α, IFN-γ, IL-1β, and IL-4 was significantly decreased in the exercise group compared to the control group. There was no difference in IL-6, IL-8, and IL-10 mRNA expression between groups. The results in the current study demonstrate that short-term moderate-intensity endurance exercise alters WBC levels and mRNA cytokine expression in leukocytes and may have a meaningful effect on immune health in dogs.

Resistance and Endurance Exercise Training Induce Differential Changes in Gut Microbiota Composition in Murine Models

Background: The effect of resistance training on gut microbiota composition has not been explored, despite the evidence about endurance exercise. The aim of this study was to compare the effect of resistance and endurance training on gut microbiota composition in mice.Methods: Cecal samples were collected from 26 C57BL/6N mice, divided into three groups: sedentary (CTL), endurance training on a treadmill (END), and resistance training on a vertical ladder (RES). After 2 weeks of adaption, mice were trained for 4 weeks, 5 days/week. Maximal endurance and resistance capacity test were performed before and after training. Genomic DNA was extracted and 16S Ribosomal RNA sequenced for metagenomics analysis. The percentages for each phylum, class, order, family, or genus/species were obtained using an open-source bioinformatics pipeline.Results: END showed higher diversity and evenness. Significant differences among groups in microbiota composition were only observed at genera and species level. END showed a significantly higher relative abundance of Desulfovibrio and Desulfovibrio sp., while Clostridium and C. cocleatum where higher for RES. Trained mice showed significantly lower relative abundance of Ruminococcus gnavus and higher of the genus Parabacteroides compared to CTL. We explored the relationship between relative taxa abundance and maximal endurance and resistance capacities after the training period. Lachnospiraceae and Lactobacillaceae families were negatively associated with endurance performance, while several taxa, including Prevotellaceae family, Prevotella genus, and Akkermansia muciniphila, were positively correlated. About resistance performance, Desulfovibrio sp. was negatively correlated, while Alistipes showed a positive correlation.Conclusion: Resistance and endurance training differentially modify gut microbiota composition in mice, under a high-controlled environment. Interestingly, taxa associated with anti- and proinflammatory responses presented the same pattern after both models of exercise. Furthermore, the abundance of several taxa was differently related to maximal endurance or resistance performance, most of them did not respond to training.

Exercise Preconditioning Blunts Early Atrogenes Expression and Atrophy in Gastrocnemius Muscle of Hindlimb Unloaded Mice

A large set of FoxOs-dependent genes play a primary role in controlling muscle mass during hindlimb unloading. Mitochondrial dysfunction can modulate such a process. We hypothesized that endurance exercise before disuse can protect against disuse-induced muscle atrophy by enhancing peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) expression and preventing mitochondrial dysfunction and energy-sensing AMP-activated protein kinase (AMPK) activation. We studied cross sectional area (CSA) of muscle fibers of gastrocnemius muscle by histochemistry following 1, 3, 7, and 14 days of hindlimb unloading (HU). We used Western blotting and qRT-PCR to study mitochondrial dynamics and FoxOs-dependent atrogenes’ expression at 1 and 3 days after HU. Preconditioned animals were submitted to moderate treadmill exercise for 7 days before disuse. Exercise preconditioning protected the gastrocnemius from disuse atrophy until 7 days of HU. It blunted alterations in mitochondrial dynamics up to 3 days after HU and the expression of most atrogenes at 1 day after disuse. In preconditioned mice, the activation of atrogenes resumed 3 days after HU when mitochondrial dynamics, assessed by profusion and pro-fission markers (mitofusin 1, MFN1, mitofusin 2, MFN2, optic atrophy 1, OPA1, dynamin related protein 1, DRP1 and fission 1, FIS1), PGC1α levels, and AMPK activation were at a basal level. Therefore, the normalization of mitochondrial dynamics and function was not sufficient to prevent atrogenes activation just a few days after HU. The time course of sirtuin 1 (SIRT1) expression and content paralleled the time course of atrogenes’ expression. In conclusion, seven days of endurance exercise counteracted alterations of mitochondrial dynamics and the activation of atrogenes early into disuse. Despite the normalization of mitochondrial dynamics, the effect on atrogenes’ suppression died away within 3 days of HU. Interestingly, muscle protection lasted until 7 days of HU. A longer or more intense exercise preconditioning may prolong atrogenes suppression and muscle protection.

Endurance exercise training-attenuated diabetic kidney disease with muscle weakness in spontaneously diabetic Torii fatty rats.

Background The aim of this study was to evaluate protective effects of endurance exercise training against diabetic kidney disease (DKD) with muscle weakness by using male spontaneously diabetic Torii (SDT) fatty rats as type 2 diabetic animal models with obesity, hypertension, and hyperlipidemia. Methods Eight-week-old SDT fatty rats (n = 12) and Sprague–Dawley (SD) rats (n = 10) were randomly divided into exercise (Ex; SDT-Ex: n = 6, SD-Ex: n = 5) and sedentary groups (SDT-Cont: n = 6, SD-Cont: n = 5), respectively. Each group underwent regular treadmill exercise four times a week from ages 8 to 16 weeks. Results The exercise attenuated hypertension and hyperlipidemia and prevented increases in renal parameter levels without affecting blood glucose levels. In the SDT fatty rats, it prevented induction of renal morphological abnormalities in the interstitium of the superficial and intermediate layers of the cortex. Downregulated expression of endothelial nitric oxide synthase in the glomerulus of the SDT fatty rats was significantly upregulated by the exercise. The exercise upregulated the renal expressions of both medium-chain acyl-CoA dehydrogenase and peroxisome proliferator-activated receptor γ coactivator-1α related to fatty acid metabolism. It increased muscle strength and both muscle weight and cross-sectional area of type IIb muscle fibers in the extensor digitorum longus muscle in the SDT fatty rats. Conclusion Endurance exercise training in type 2 diabetes ameliorates DKD by improving endothelial abnormality and enhancing fatty acid metabolism in addition to attenuated hypertension, hyperlipidemia, and muscle weakness independently of blood glucose levels.

Nanocurcumin potential to increase mitochondrial biogenesis in skeletal muscle via AMPK-PGC-1alpha

Curcumin, which comes from the rhizome Curcuma longa L, is known as the polyphenol with a high level content of natural antioxidants and has benefits on pharmacological activities and human health. The purpose of current study was to investigate the effect of nanocurcumin itself and the combination with exercise on 5' adenosine monophosphate-activated protein kinase (AMPK), PGC-1α, and mitochondrial protein expression of cytochrome c oxidase subunit IV (COX-IV), in rat gastrocnemius muscle. Animals separated to be non-endurance exercise and endurance exercise group. Curcumin and nanocurcumin with doses 100 mg per kg-body weight per day were given peroral in both groups for 28 days in order to determine the effect of nanocurcumin on mitochondrial markers including AMPK-PGC-1α and COX-IV. Western blotting (WB) method was applied to investigate the protein expression on skeletal muscle. The result showed that nanocurcumin increased mitochondrial marker protein COX-IV on non exercise and exercise groups. Furthermore, our result demonstrated that nanocurcumin treatment combined with exercise increased the phosphorylation of AMPK and PGC-1α. Addition, nanocurcumin treatment alone, without exercise, also increased PGC-1α protein expression. This current result suggests that nanocurcumin could increase mitochondrial biogenesis markers. When it is used together with exercise, it potentially has the additive effect of exercise to increase mitochondrial markers through AMPK-PGC-1α signaling pathway. In conclusion, nanocurcumin treatment combined with exercise potentially increases mitochondrial biogenesis.

Acute impact of an endurance race on biventricular and biatrial myocardial strain in competitive male and female triathletes evaluated by feature-tracking CMR

Objectives Cardiac adaptation in endurance athletes is a well-known phenomenon, but the acute impact of strenuous exercise is rarely reported on. The aim of this study was to analyze the alterations in biventricular and biatrial function in triathletes after an endurance race using novel feature-tracking cardiac magnetic resonance (FT-CMR). Methods Fifty consecutive triathletes (45 ± 10 years; 80% men) and twenty-eight controls were prospectively recruited, and underwent 1.5-T CMR. Biventricular and biatrial volumes, left ventricular ejection fraction (LVEF), FT-CMR analysis, and late gadolinium imaging (LGE) were performed. Global systolic longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were assessed. CMR was performed at baseline and following an endurance race. High-sensitive troponin T and NT-proBNP were determined. The time interval between race completion and CMR was 2.3 ± 1.1 h (range 1–5 h). Results Post-race troponin T (p < 0.0001) and NT-proBNP (p < 0.0001) were elevated. LVEF remained constant (62 ± 6 vs. 63 ± 7%, p = 0.607). Post-race LV GLS decreased by tendency (− 18 ± 2 vs. − 17 ± 2%, p = 0.054), whereas GCS (− 16 ± 4 vs. − 18 ± 4%, p < 0.05) and GRS increased (39 ± 11 vs. 44 ± 11%, p < 0.01). Post-race right ventricular GLS (− 19 ± 3 vs. − 19 ± 3%, p = 0.668) remained constant and GCS increased (− 7 ± 2 vs. − 8 ± 3%, p < 0.001). Post-race left atrial GLS (30 ± 8 vs. 24 ± 6%, p < 0.0001) decreased while right atrial GLS remained constant (25 ± 6 vs. 24 ± 6%, p = 0.519). Conclusions The different alterations of post-race biventricular and biatrial strain might constitute an intrinsic compensatory mechanism following an acute bout of endurance exercise. The combined use of strain parameters may allow a better characterization of ventricular and atrial function in endurance athletes. Key Points • Triathletes demonstrate a decrease of LV global longitudinal strain by tendency and constant RV global longitudinal strain following an endurance race. • Post-race LV and RV global circumferential and radial strains increase, possibly indicating a compensatory mechanism after an acute endurance exercise bout. • Subgroup analyses of male triathletes with focal myocardial fibrosis did not demonstrate alterations in biventricular and biatrial strain after an endurance race.

Addendum: Hackney, A.C.; Willett, H.N. Testosterone Responses to Intensive, Prolonged Endurance Exercise in Women. Endocrines 2020, 1, 119–124

It has been brought to our attention that the Ethics Committee and approval code were missing in the Materials and Methods Section of our published paper [...]

Endurance exercise ameliorates phenotypes in Drosophila models of Spinocerebellar Ataxias

Endurance exercise is a potent intervention with widespread benefits proven to reduce disease incidence and impact across species. While endurance exercise supports neural plasticity, enhanced memory, and reduced neurodegeneration, less is known about the effect of chronic exercise on the progression of movement disorders such as ataxias. Here, we focused on three different types of ataxias, Spinocerebellar Ataxias Type (SCAs) 2, 3, and 6, belonging to the polyglutamine (polyQ) family of neurodegenerative disorders. In Drosophila models of these SCAs, flies progressively lose motor function. Here, we observe marked protection of speed and endurance in exercised SCA2 flies and modest protection in exercised SCA6 models, while no benefit is observed in SCA3 flies. Causative protein levels are reduced in SCA2 flies after chronic exercise, but not in SCA3 models, linking protein levels to exercise-based benefits. Additional investigations indicate that the exercise-inducible protein, Sestrin (Sesn) suppresses mobility decline and improves early death in SCA2 flies, even without exercise, coincident with disease protein level reduction and increased autophagic flux. These improvements depend on previously established functions of Sesn that reduce oxidative damage and modulate mTOR activity. Our study suggests differential responses of polyQ SCAs to exercise, highlighting the potential for more extensive application of exercise-based therapies in the prevention of polyQ neurodegeneration. Defining the mechanisms by which endurance exercise suppresses polyQ SCAs will open the door for more effective treatment for these diseases.