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.

Systematic Review and Meta-Analysis of Endurance Exercise Training Protocols for Mice

Inbred and genetically modified mice are frequently used to investigate the molecular mechanisms responsible for the beneficial adaptations to exercise training. However, published paradigms for exercise training in mice are variable, making comparisons across studies for training efficacy difficult. The purpose of this systematic review and meta-analysis was to characterize the diversity across published treadmill-based endurance exercise training protocols for mice and to identify training protocol parameters that moderate the adaptations to endurance exercise training in mice. Published studies were retrieved from PubMed and EMBASE and reviewed for the following inclusion criteria: inbred mice; inclusion of a sedentary group; and exercise training using a motorized treadmill. Fifty-eight articles met those inclusion criteria and also included a “classical” marker of training efficacy. Outcome measures included changes in exercise performance, V˙O2max, skeletal muscle oxidative enzyme activity, blood lactate levels, or exercise-induced cardiac hypertrophy. The majority of studies were conducted using male mice. Approximately 48% of studies included all information regarding exercise training protocol parameters. Meta-analysis was performed using 105 distinct training groups (i.e., EX-SED pairs). Exercise training had a significant effect on training outcomes, but with high heterogeneity (Hedges’ g=1.70, 95% CI=1.47–1.94, Tau2=1.14, I2=80.4%, prediction interval=−0.43–3.84). Heterogeneity was partially explained by subgroup differences in treadmill incline, training duration, exercise performance test type, and outcome variable. Subsequent analyses were performed on subsets of studies based on training outcome, exercise performance, or biochemical markers. Exercise training significantly improved performance outcomes (Hedges’ g=1.85, 95% CI=1.55–2.15). Subgroup differences were observed for treadmill incline, training duration, and exercise performance test protocol on improvements in performance. Biochemical markers also changed significantly with training (Hedges’ g=1.62, 95% CI=1.14–2.11). Subgroup differences were observed for strain, sex, exercise session time, and training duration. These results demonstrate there is a high degree of heterogeneity across exercise training studies in mice. Training duration had the most significant impact on training outcome. However, the magnitude of the effect of exercise training varies based on the marker used to assess training efficacy.

Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training

Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (Si) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on Si. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline Si and ∆Si, focused around cholinergic signalling, including downstream calcium and chemokine signalling. The identification of calcium regulated MEF2A transcription factor as the most statistically significant candidate driving the transcriptional signature associated to ∆Si further strengthens the relevance of calcium signalling in EET mediated Si response.

High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity

One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, p=0.0003) and reduced Ac-SDKP levels (by 50%, p<0.0001). T2 increased the number of hematopoietic stem cells (~200%, p=0.0008), early erythroid progenitor colonies (~300%, p<0.0001) and reticulocytes (~500%, p=0.0007), and reduced erythrocyte lifespan (~50%, p=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril treatment: 10 mg.kg-1.d-1). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated to increased ACE NH2-terminal activity and reduction of the hematopoietic inhibitor Ac-SDKP.

The Impact of Fitness Status on Vascular and Baroreceptor Function in Healthy Women and Men

<b><i>Background:</i></b> Chronic endurance exercise training elicits desirable physiological adaptations in the cardiovascular system. The volume of exercise training required to generate healthy adaptations is unclear. This study assessed the effects of differing exercise training levels on arterial stiffness, compliance, and autonomic function. <b><i>Methods:</i></b> Eighty healthy adults (38.5 ± 9.7 years; 44% female) defined as endurance-trained (ET, <i>n</i> = 29), normally active (NA, <i>n</i> = 27), or inactive (IN, <i>n</i> = 24) participated. Cardiovascular markers, including hemodynamics, large arterial compliance and small arterial compliance (LAC and SAC), carotid-femoral pulse wave velocity (PWV), and spontaneous baroreceptor sensitivity (BRS) were assessed. <b><i>Results:</i></b> ET showed significantly greater LAC values (21.4 ± 6.5) than NA (16.9 ± 2.5; <i>p</i> = 0.002) and IN (14.7 ± 3.2 mL × mm Hg × 10; <i>p</i> = 0.028). Values for SAC and BRS were significantly higher in ET than IN (<i>p</i> &#x3c; 0.001 and <i>p</i> = 0.028, respectively), but not NA. Compared to IN, PWV values for ET and NA were significantly lower (<i>p</i> &#x3c; 0.003). After adjusting for covariates (age, sex, and SBP), significant associations with cardiovascular fitness status were noted for all markers but BRS. <b><i>Conclusion:</i></b> Endurance exercise increases LAC likely due to high-volume training; however, lower volumes of physical activity may be sufficient to positively benefit vascular health overall.

Exercise Pills for Drug Addiction: Forced Moderate Endurance Exercise Inhibits Methamphetamine-Induced Hyperactivity through the Striatal Glutamatergic Signaling Pathway in Male Sprague Dawley Rats

Physical exercise reduces the extent, duration, and frequency of drug use in drug addicts during the drug initiation phase, as well as during prolonged addiction, withdrawal, and recurrence. However, information about exercise-induced neurobiological changes is limited. This study aimed to investigate the effects of forced moderate endurance exercise training on methamphetamine (METH)-induced behavior and the associated neurobiological changes. Male Sprague Dawley rats were subjected to the administration of METH (1 mg/kg/day, i.p.) and/or forced moderate endurance exercise (treadmill running, 21 m/min, 60 min/day) for 2 weeks. Over the two weeks, endurance exercise training significantly reduced METH-induced hyperactivity. METH and/or exercise treatment increased striatal dopamine (DA) levels, decreased p(Thr308)-Akt expression, and increased p(Tyr216)-GSK-3β expression. However, the phosphorylation levels of Ser9-GSK-3β were significantly increased in the exercise group. METH administration significantly increased the expression of NMDAr1, CaMKK2, MAPKs, and PP1 in the striatum, and exercise treatment significantly decreased the expression of these molecules. Therefore, it is apparent that endurance exercise inhibited the METH-induced hyperactivity due to the decrease in GSK-3β activation by the regulation of the striatal glutamate signaling pathway.

Endurance exercise training suppresses Parkinson disease-induced overexpression of apoptotic mediators in the heart

BACKGROUND We have shown elevated levels of p53 and active caspase-3 in the heart with Parkinson disease (PD). The main aim of this study is to examine the effect of treadmill training on the cardiac expression of p53 and active caspase-3 in the mouse with induced Parkinsonism. METHODS: Thirty randomly selected normal albino mice were equally divided into the following 3 groups: sedentary control (SC), sedentary Parkinson diseased (SPD), and exercised Parkinson diseased (EPD). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p) were used to induce chronic Parkinson disease in the SPD and EPD animals. The expression of p53 and active caspase-3 was investigated, using immunohistochemistry, in the heart in each animal group. RESULTS: Both p53 and active caspase-3 expression was significantly (p value < 0.05) reduced in the PD heart following endurance exercise training. CONCLUSION: Our present data suggest that chronic exercise training reduced PD-induced upregulation of p53 and active caspase-3 in the heart. Thus, our study suggests that inhibiting p53 and/or active caspase-3 may be considered as a therapeutic approach to ameliorate PD cardiomyopathy.