Weeks Of Treadmill Exercise Training Research Articles

Exercise ameliorates muscular excessive mitochondrial fission, insulin resistance and inflammation in diabetic rats via irisin/AMPK activation

This study aimed to investigate the effects of exercise on excessive mitochondrial fission, insulin resistance, and inflammation in the muscles of diabetic rats. The role of the irisin/AMPK pathway in regulating exercise effects was also determined. Thirty-two 8-week-old male Wistar rats were randomly divided into four groups (n = 8 per group): one control group (Con) and three experimental groups. Type 2 diabetes mellitus (T2DM) was induced in the experimental groups via a high-fat diet followed by a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 30 mg/kg body weight. After T2DM induction, groups were assigned as sedentary (DM), subjected to 8 weeks of treadmill exercise training (Ex), or exercise training combined with 8-week cycloRGDyk treatment (ExRg). Upon completion of the last training session, all rats were euthanized and samples of fasting blood and soleus muscle were collected for analysis using ELISA, immunofluorescence, RT-qPCR, and Western blotting. Statistical differences between groups were analyzed using one-way ANOVA, and differences between two groups were assessed using t-tests. Our findings demonstrate that exercise training markedly ameliorated hyperglycaemia, hyperlipidaemia, and insulin resistance in diabetic rats (p < 0.05). It also mitigated the disarranged morphology and inflammation of skeletal muscle associated with T2DM (p < 0.05). Crucially, exercise training suppressed muscular excessive mitochondrial fission in the soleus muscle of diabetic rats (p < 0.05), and enhanced irisin and p-AMPK levels significantly (p < 0.05). However, exercise-induced irisin and p-AMPK expression were inhibited by cycloRGDyk treatment (p < 0.05). Furthermore, the administration of CycloRGDyk blocked the effects of exercise training in reducing excessive mitochondrial fission and inflammation in the soleus muscle of diabetic rats, as well as the positive effects of exercise training on improving hyperlipidemia and insulin sensitivity in diabetic rats (p < 0.05). These results indicate that regular exercise training effectively ameliorates insulin resistance and glucolipid metabolic dysfunction, and reduces inflammation in skeletal muscle. These benefits are partially mediated by reductions in mitochondrial fission through the irisin/AMPK signalling pathway.

Moderate exercise-induced dynamics on key sepsis-associated signaling pathways in the liver

BackgroundThere is a clear relationship between quantitative measures of fitness (e.g., VO2 max) and outcomes after surgical procedures. Whether or not fitness is a modifiable risk factor and what underlying biological processes drive these changes are not known. The purpose of this study was to evaluate the moderate exercise training effect on sepsis outcomes (survival) as well as the hepatic biological response. We chose to study the liver because it plays a central role in the regulation of immune defense during systemic infection and receives blood flow directly from the origin of infection (gut) in the cecal ligation and puncture (CLP) model.MethodsWe randomized 50 male (♂) and female (♀) Sprague–Dawley rats (10 weeks, 340 g) to 3 weeks of treadmill exercise training, performed CLP to induce polymicrobial “sepsis,” and monitored survival for five days (Part I). In parallel (Part II), we randomized 60 rats to control/sedentary (G1), exercise (G2), exercise + sham surgery (G3), CLP/sepsis (G4), exercise + CLP [12 h (G5) and 24 h (G6)], euthanized at 12 or 24 h, and explored molecular pathways related to exercise and sepsis survival in hepatic tissue and serum.ResultsThree weeks of exercise training significantly increased rat survival following CLP (polymicrobial sepsis). CLP increased inflammatory markers (e.g., TNF-a, IL-6), which were attenuated by exercise. Sepsis suppressed the SOD and Nrf2 expression, and exercise before sepsis restored SOD and Nrf2 levels near the baseline. CLP led to increased HIF1a expression and oxidative and nitrosative stress, the latter of which were attenuated by exercise. Haptoglobin expression levels were increased in CLP animals, which was significantly amplified in exercise + CLP (24 h) rats.ConclusionsModerate exercise training (3 weeks) increased the survival in rats exposed to CLP, which was associated with less inflammation, less oxidative and nitrosative stress, and activation of antioxidant defense pathways.Graphical abstract

Quantitative Proteomics Identifies Novel Nrf2-Mediated Adaptative Signaling Pathways in Skeletal Muscle Following Exercise Training.

Exercise training (ExT) improves skeletal muscle health via multiple adaptative pathways. Nrf2 is a principal antioxidant transcription factor responsible for maintaining intracellular redox homeostasis. In this study, we hypothesized that Nrf2 is essential for adaptative responses to ExT and thus beneficial for muscle. Experiments were carried out on male wild type (WT) and iMS-Nrf2flox/flox inducible muscle-specific Nrf2 (KO) mice, which were randomly assigned to serve as sedentary controls (Sed) or underwent 3 weeks of treadmill ExT thus generating four groups: WT-Sed, WT-ExT, KO-Sed, and KO-ExT groups. Mice were examined for exercise performance and in situ tibialis anterior (TA) contractility, followed by mass spectrometry-based proteomics and bioinformatics to identify differentially expressed proteins and signaling pathways. We found that maximal running distance was significantly longer in the WT-ExT group compared to the WT-Sed group, whereas this capacity was impaired in KO-ExT mice. Force generation and fatigue tolerance of the TA were enhanced in WT-ExT, but reduced in KO-ExT, compared to Sed controls. Proteomic analysis further revealed that ExT upregulated 576 proteins in WT but downregulated 207 proteins in KO mice. These proteins represent pathways in redox homeostasis, mitochondrial respiration, and proteomic adaptation of muscle to ExT. In summary, our data suggest a critical role of Nrf2 in the beneficial effects of SkM and adaptation to ExT.

Exercise training counteracts the cardiac metabolic remodelling induced by experimental pulmonary arterial hypertension

Exercise training provides several cardiovascular benefits in both physiological and pathological conditions; however, its use as a therapeutic tool for pulmonary arterial hypertension (PAH) has been poorly explored. This study aimed to extend the comprehension of the cardioprotective effects of exercise training in the set of PAH focusing on the metabolic changes promoted by exercise in the right ventricle (RV). The monocrotaline animal model of PAH was used and male Wistar rats were submitted to two weeks of treadmill exercise training (5 days/week, 60 min/day, 25 m/min) following disease establishment. Trained rats showed an improved diastolic function (lower end-diastolic pressure and tau) despite the presence of cardiac overload (increased peak systolic pressure, end-diastolic pressure and arterial elastance). This enhanced hemodynamic response was paralleled by an increased uptake of glucose to cardiomyocytes through glucose transporter type 4 (GLUT4) followed by increased lactate dehydrogenase (LDH) activity. Exercise did not reverse the decrease of fatty acid oxidation related to PAH but increased the content of the transcription factors peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Two weeks of exercise did not modulate the changes in amino acid metabolism secondary to PAH. Our work suggests that continuous aerobic exercise of moderate intensity, despite its short-term duration and application in a late stage of the disease, supports the RV response to PAH by promoting a shift in the cardiac metabolic phenotype.

Twelve weeks of treadmill exercise training with green tea extract reduces myocardial oxidative stress and alleviates cardiomyocyte apoptosis in aging rat: The emerging role of BNIP3 and HIF-1α/IGFBP3 pathway.

In this study, we consider the effect of treadmill exercise training, green tea extract, and combination of exercise training with green tea extract, in aging rat cardiac myocytes apoptosis markers (i.e., HIF-1α, BNIP3, Bax, IGFBP3, Bcl-2, caspase-3, MDA, GPx, Bax/Bcl-2 ratio, and hematoxylin and eosin). Twenty-four rats (male, Wistar) were divided into four groups: (I) control (n= 6), (II) green tea extract (n= 6), (III) exercise (n= 6), and (IV) exercise + green tea extract (n= 6). Exercise groups performed 12 weeks of running on a rodent treadmill at 17-27 m.min-1 (60-75% vo2peak) for 5 days per week. Green tea extract involved 300 mg.kg-1 , 5 days per week for 12 weeks. After being euthanized, the blood and heart were collected for glutathione peroxidase (GPx) activity, malondialdehyde (MDA), HIF-1α, BNIP3, insulin-like growth factor-binding protein-3 (IGFBP3), Bax, Bcl-2, caspase-3, Bax/Bcl-2 ratio, and hematoxylin and eosin level measurements. Compared to control, the ANOVA demonstrated significant effects of green tea extract (F=14.646 to 32.453, p= .009 to .001, η=0.295 to 0.715) and exercise training (F=9.213 to 133.828, p= .007 to .001, η=0.315 to η=0.870) on HIF-1a, BNIP3, Bax, IGFBP3, Bcl-2, caspase-3, MDA, GPx, and Bax/Bcl-2 ratio. However, the combination of green tea extract and exercise had no effect on the aforementioned apoptosis markers when compared to isolated green tea extract or isolated exercise (F=0.002 to 4.068, p= .057 to .968, and η=0.001 to 0.169). PRACTICAL APPLICATIONS: Isolated exercise training and green tea extract may provide a cardioprotective effect on aging-induced apoptosis through the downregulation of HIF-1α, BNIP3, and IGFBP3 in the heart muscle. However, further research is needed to clarify the effects of combining exercise and green tea.

Mitochondrial Function in High-Fat Fed and Exercise-Trained Mice Unable to Induce Autophagy

Impaired mitochondrial lipid respiration is implicated in obesity-induced insulin resistance but can be enhanced with exercise training. Autophagy is involved in remodeling the mitochondrial proteome and may be required for mitochondrial and whole-body adaptations in lipid respiration. We used a diet-induced obesity model of C57BL/6J mice and investigated the requirement of autophagy for mitochondrial adaptations to 8 weeks of treadmill exercise training using transgenic mice that cannot induce autophagy with exercise (BCL) compared to wild type controls (WT, n=3-5). High fat (HF) fed mice had lower glucose tolerance at 4 weeks compared to low fat (LF, ∼35%, P&amp;lt;0.01), regardless of genotype. After 8 weeks of exercise, LF-BCL mice had similar glucose tolerance to LF-WT mice. However, the HF-BCL mice had lower glucose tolerance compared to HF-WT mice (∼19%, P&amp;lt;0.01) suggesting a blunted improvement in glucose tolerance following training in the absence of autophagy. At week 12, mitochondria were isolated from quadriceps for respirometry. Oxidative phosphorylation capacity was normalized to electron transport system capacity. Lipid supported respiration (octanoyl-carnitine) was higher in the HF mice compared to LF (∼17%, P&amp;lt;0.01) and the lack of autophagy activation had no effect. Glutamate-malate-succinate supported respiration was lower in BCL mice compared to WT (∼11%, P&amp;lt;0.05), but only on a LF diet suggesting the requirement of autophagy for improved mitochondrial function with exercise may vary between substrates. Whole body respiratory exchange ratio was measured during 24 hours of fasting and all mice shifted to lipid oxidation with no difference between diet or genotype (P = 0.11). Collectively, skeletal muscle mitochondrial lipid oxidation was greater with HF, despite glucose intolerance. The activation of autophagy with exercise was not required for mitochondrial lipid adaptations or whole body metabolic flexibility, but may be required for non-lipid substrates. Disclosure S.E. Ehrlicher: None. H.D. Stierwalt: None. S.A. Newsom: None. M.M. Robinson: None.

The effects of exercise on depressive- and anxiety-like behaviors as well as lung and hippocampus oxidative stress in ovalbumin-sensitized juvenile rats

Allergic asthma during early life period has been reported to be associated with neurochemical and behavioral disorders, including anxiety and depression. We aimed to determine the effects of exercise on depressive- and anxiety-like behaviors as well as lung and hippocampus oxidative stress in ovalbumin (OVA)-sensitized juvenile rats. Animals were divided into 4 groups including control (non-exercised and non-sensitized), Exe (exercise and non-sensitized); OVA (non-exercised and OVA-sensitized); and OVA+Exe (exercised and OVA-sensitized). The rats were subjected to chronic OVA sensitization followed by 4 weeks of treadmill exercise training. Compared to the control group, the OVA group had an increase in anxiety- and depressive-like behavior, lung inflammation, and oxidative stress index in the lung and hippocampus. Compared to the OVA group, the OVA+Exe group had a decline in anxiety- and depressive-like behavior, lung inflammation, and oxidative stress index in the lung and hippocampus. No significant difference in terms of the above-mentioned parameters, were found between the control group and the Exe group. Exercise decreased depressive- and anxiety-like behaviors in OVA-sensitized juvenile rats; this effect might have been mainly mediated by improvement in antioxidant system.

Effect of exercise training on liver antioxidant enzymes in STZ-diabetic rats.

Abstract Aims Although exercise is shown to improve the antioxidant defense in many organs and pathologies, little research has focused on the effect of chronic exercise training on diabetes-induced liver oxidative stress. We evaluated the effect of chronic treadmill exercise on the hepatic antioxidant enzymes and redox status in STZ-diabetic rats. Main methods Male Wistar rats were randomly assigned into control, trained, diabetic, and diabetic trained groups. Type 1 diabetes mellitus was induced via intraperitoneal injection of STZ. The animals were trained by running on a non-graded motorized treadmill 5 days weekly for a period of 9 weeks. The activity and mRNA levels of antioxidant enzymes, hydrogen peroxide generation, thiol content, and GSH/GSSG ratio were evaluated. Key findings Diabetes negatively affected the hepatic antioxidant defense as indicated by reduced SOD activity, downregulation of SOD1 and GPX1 mRNA levels, increased catalase activity, increased H2O2 production, reduced thiol content and GSH/GSSG ratio. Nine weeks of treadmill exercise training either prevented (SOD1 mRNA, GPX1 mRNA, and thiol content) or ameliorated (catalase activity, SOD activity, H2O2 generation, GSH/GSSG ratio) these diabetes hepatic effects. Significance Our data suggest that exercise training attenuates the diabetes-induced alterations on antioxidant enzymes in the liver of STZ-diabetic rats by improving the hepatic ROS scavenging and redox status. This result strongly implicates a positive effect of exercise training on diabetes-induced liver oxidative stress.

Functional changes in deep dorsal horn interneurons following spinal cord injury are enhanced with different durations of exercise training.

Exercise training after spinal cord injury (SCI) enhances collateral sprouting from axons near the injury and is thought to promote intraspinal circuit reorganisation that effectively bridges the SCI. The effects of exercise training, and its duration, on interneurons in these de novo intraspinal circuits are poorly understood. In an adult mouse hemisection model of SCI, we used whole-cell patch-clamp electrophysiology to examine changes in the intrinsic and synaptic properties of deep dorsal horn interneurons in the vicinity of a SCI in response to the injury, and after 3 and 6 weeks of treadmill exercise training. SCI alone exerted powerful effects on the intrinsic and synaptic properties of interneurons near the lesion. Importantly, synaptic activity, both local and descending, was preferentially enhanced by exercise training, suggesting that exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI. Following incomplete spinal cord injury (SCI), collaterals sprout from intact and injured axons in the vicinity of the lesion. These sprouts are thought to form new synaptic contacts that effectively bypass the lesion epicentre and contribute to improved functional recovery. Such anatomical changes are known to be enhanced by exercise training; however, the mechanisms underlying exercise-mediated plasticity are poorly understood. Specifically, we do not know how SCI alone or SCI combined with exercise alters the intrinsic and synaptic properties of interneurons in the vicinity of a SCI. Here we use a hemisection model of incomplete SCI in adult mice and whole-cell patch-clamp recording in a horizontal spinal cord slice preparation to examine the functional properties of deep dorsal horn (DDH) interneurons located in the vicinity of a SCI following 3 or 6 weeks of treadmill exercise training. We examined the functional properties of local and descending excitatory synaptic connections by recording spontaneous excitatory postsynaptic currents (sEPSCs) and responses to dorsal column stimulation, respectively. We find that SCI in untrained animals exerts powerful effects on intrinsic, and especially, synaptic properties of DDH interneurons. Plasticity in intrinsic properties was most prominent at 3 weeks post SCI, whereas synaptic plasticity was greatest at 6 weeks post injury. Exercise training did not markedly affect intrinsic membrane properties; however, local and descending excitatory synaptic drive were enhanced by 3 and 6 weeks of training. These results suggest exercise promotes synaptic plasticity in spinal cord interneurons that are ideally placed to form new intraspinal circuits after SCI.

Exercise Training does not Enhance Hypothalamic Responsiveness to Leptin or Ghrelin in Male Mice

The detection of hormone and nutrient signals by the hypothalamus is blunted in obesity and contributes to dysregulated energy homeostasis. We investigated whether aerobic exercise training would improve long-term hypothalamic sensitivity to both leptin and ghrelin, independent of acute exercise-induced signalling. Male C57Bl/6J mice were fed either a chow or high-fat diet for 6 weeks, then remained sedentary on their respective diet, or completed 6 weeks of treadmill exercise training with a progressive increase in exercise volume and intensity. Food intake and hypothalamic signalling were assessed in mice injected with leptin or ghrelin at least 24 h after the last exercise bout. Exercise training reduced body mass, increased daily food intake and improved glucose tolerance. Intraperitoneal leptin administration reduced food intake in lean and obese mice, and this was not enhanced after exercise training. Leptin-mediated activation of phosphorylated signal transducer and activator of transcription 3 in the arcuate nucleus and ventromedial nucleus of the hypothalamus was not enhanced with exercise training. Ghrelin increased food intake and c-Fos positive neurones in the hypothalamus in lean and obese mice, and these physiological and molecular responses were not enhanced with exercise training. This suggests that the previously reported exercise effects on sensitising hypothalamic signalling and food intake responses may be limited to the period immediately after an exercise bout, and are not a result of stable structural or molecular changes that occur with exercise training.

Aerobic exercise attenuates inhibitory avoidance memory deficit induced by paradoxical sleep deprivation in rats

The deleterious effects of paradoxical sleep deprivation (SD) on memory processes are well documented. Physical exercise improves many aspects of brain functions and induces neuroprotection. In the present study, we investigated the influence of 4 weeks of treadmill aerobic exercise on both long-term memory and the expression of synaptic proteins (GAP-43, synapsin I, synaptophysin, and PSD-95) in normal and sleep-deprived rats. Adult Wistar rats were subjected to 4 weeks of treadmill exercise training for 35min, five times per week. Twenty-four hours after the last exercise session, the rats were sleep-deprived for 96h using the modified multiple platform method. To assess memory after SD, all animals underwent training for the inhibitory avoidance task and were tested 24h later. The aerobic exercise attenuated the long-term memory deficit induced by 96h of paradoxical SD. Western blot analysis of the hippocampus revealed increased levels of GAP-43 in exercised rats. However, the expression of synapsin I, synaptophysin, and PSD-95 was not modified by either exercise or SD. Our results suggest that an aerobic exercise program can attenuate the deleterious effects of SD on long-term memory and that this effect is not directly related to changes in the expression of the pre- and post-synaptic proteins analyzed in the study.

Resveratrol Attenuates Exercise-Induced Adaptive Responses in Rats Selectively Bred for Low Running Performance

Low capacity runner (LCR) rats have been developed by divergent artificial selection for treadmill endurance capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running. In this study it was examined whether 12 weeks of treadmill exercise training and/or resveratrol can retrieve the low running performance of the LCR and impact mitochondrial biogenesis and quality control. Resveratrol regressed running performance in trained LCR (p<0.05). Surprisingly, exercise and resveratrol treatments significantly decreased pAMPK/AMPK, SIRT1, SIRT4, forkhead transcription factor 1 (FOXO1) and mitochondrial transcription factor A (TFAM) levels in these animals (p<0.05). Mitochondrial fusion protein, HSP78 and polynucleotide phosphorylase were significantly induced in LCR-trained, LCR-resveratrol treated, LCR-trained and resveratol treated groups compared to LCR-controls. The data indicate that the AMPK-SIRT1-NAMPT-FOXO1 axis could be important to the limited aerobic endurance capacity of low running capacity rats. Resveratrol supplementation was not beneficial in terms of aerobic endurance performance, mitochondrial biogenesis, or quality control.

Exercise Training (ExT) Normalizes Subfornical Organ (SFO)‐ Mediated Sympathoexcitation in Chronic Heart Failure (HF)

ExT normalizes sympathoexcitation (SymEx) exhibited in HF, however the underlying mechanisms are not clear. The SFO is involved in dictating SymEx and is influenced by peptides such as angiotensin (Ang) II due to its weak blood‐brain barrier. We hypothesized that neuronal activity in the SFO would be enhanced in HF and contribute to increased Ang II‐mediated SymEx, and that ExT would reverse this process. HF induced by coronary artery ligation in Sprague‐Dawley rats was confirmed by echocardiography 4 weeks after surgery. HF rats displayed increased neuronal activity in the SFO, as assessed by FosB immunohistochemistry (101 ± 9 vs. 29 ± 2 cells). This increase was attenuated after 4 weeks of treadmill ExT (36 ± 7 cells). In anesthetized rats, microinjection of Ang II into the SFO increased renal sympathetic nerve activity (RSNA) to a greater extent in HF (23 ± 3 vs. 9 ± 1%; 100 pmol), and was normalized after ExT (8 ± 2%). ExT also abolished the decrease in RSNA in HF rats after losartan microinjection into the SFO (−21 ± 4 vs. −1 ± 3%; 200 pmol), implying higher endogenous Ang II tone in HF. ExT reversed the elevated mRNA and protein expression of AT1R in the SFO of rats with HF. The enhanced activation of the SFO by elevated tonic Ang II contributes to the enhanced SymEx exhibited in HF. The reduction in AT1 receptors in the SFO by ExT may be responsible for restoring the neuronal activation in the SFO and SFO‐mediated SymEx. Supp. by NIH HL62222.

Resveratrol enhances exercise training responses in rats selectively bred for high running performance

High Capacity Runner (HCR) rats have been developed by divergent artificial selection for treadmill endurance running capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running and the antioxidant capacity of resveratrol is also demonstrated. In this study we examine whether 12 weeks of treadmill exercise training and/or resveratrol can enhance performance in HCR. Indeed, resveratrol increased aerobic performance and strength of upper limbs of these rats. Moreover, we have found that resveratrol activated the AMP-activated protein kinase, SIRT1, and mitochondrial transcription factor A (p<0.05). The changes in mitochondrial fission/fusion and Lon protease/HSP78 levels suggest that exercise training does not significantly induce damage of proteins. Moreover, neither exercise training nor resveratrol supplementation altered the content of protein carbonyls. Changes in the levels of forkhead transcription factor 1 and SIRT4 could suggest increased fat utilization and improved insulin sensitivity. These data indicate, that resveratrol supplementation enhances aerobic performance due to the activation of the AMPK-SIRT1-PGC-1α pathway.

Consumption of a high‐fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

Endurance exercise training promotes angiogenesis in the brain of chronic/progressive mouse model of Parkinson's Disease

The main goal of this study is to evaluate the effect of treadmill exercise on the angiogenesis markers in the striatum (ST) of chronic/progressive parkinsonian mice. Forty 57BL/6 albino mice were randomly divided into four groups. Sedentary control (SC, n=10), exercise control (ExC, n=10), sedentary Parkinson's (SPD, n=10), and exercised Parkinson's (ExPD, n=10). Parkinsonism was induced by the injection with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks, three days and half a part. Following the induction of parkinsonism, ExPD and ExC animal groups were trained on a modified human treadmill at a speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4~weeks. The remaining two groups (SPD and SC) were housed in cages for the same period. At the end of the experiment, the angiogenesis markers; Vascular Endothelial Growth Factor (VEGF) and CD34 were examined in the striatum in the four animal groups. PD resulted in a significant decrease in blood vessel density with the comparison between the sedentary control and PD model animals (p < 0.005). Four weeks of treadmill exercise training significantly increased angiogenesis in the striatum in ExPD groups (p < 0.05). Exercise also induced an increase in blood vessel density in the striatum of the control animals, but the change was not significant (P < 0.3). These data suggest that 4 weeks of treadmill exercise promoted angiogenesis in the brain of chronic Parkinsonian mice, which can partially explain the beneficial role exercise in patients with PD. Further studies are required to determine the mechanism of exercise-induced angiogenesis in PD.

Effects Of Endurance Exercise On Jnk, Hsp72, And Nf-kB Activation In Oletf Skeletal Muscle

Redox-sensitive kinases and HSP72 (heat shock protein) have been reported to be associated with the development and protection of type 2 diabetes, respectively. Exercise training has been proved to serve as a therapeutic method for the treatment of type 2 diabetes. However, little is known about how exercise exerts protective effect on type 2 diabetes through regulation of redox-sensitive kinase and HSP72. PURPOSE: To investigate the effect of 12 weeks of treadmill exercise training on the expression of stress kinases including JNK (c-Jun NH2-terminal kinase) and IKK (IkB kinase), HSP72, and NF-kB activation in type 2 diabetic OLETF (Otsuka Long-Evans Tokushima Fatty) rat skeletal muscle. METHODS: The OLETF rats were randomly divided into exercise training group (Ex-OLETF, n=8) and sedentary group (Sed-OLETF, n=8), and the LETO rats were used as control group (n=5). OLETF rats were aerobically trained 5 days/wk for 12 weeks at a speed of 15-21 m/min. After 48 hours the last training session, gastrocnemius muscle was removed and stored at -80°C for further analysis. RESULTS: As markers of oxidative stress, the levels of hydroperoxide and 4-HNE in OLETF groups were significantly higher compared with LETO group. There was no difference between Ex-OLETF and Sed-OLETF. Phosphorylation of IKK beta, IkB alpha, and cytosolic fraction of JNK was elevated in OLETF compared with LETO, however, there was no significant difference between Ex-OLETF and Sed-OLETF. The expression of HSP72 was downregulated in OLETF compared with LETO, but was significantly increased in Ex-OLETF compared with Sed-OLETF. NF-kB DNA binding activity in Sed-OLETF group was significantly higher compared with LETO group. Although it was not statistically significant, exercise training in Ex-OLETF group showed the trend of reducing the activation of NF-kB DNA binding activity compared with Sed-OLETF group. CONCLUSION: Our findings indicate that although oxidative stress, stress kinase activation, and lower HSP72 expression are found in OLETF skeletal muscle compared to LETO control, it appears that protective effect of exercise on type 2 diabetes would be regulated by independent of JNK and NF-kB pathway.

IMPROVED CARNITINE STATUS IN THE TRAINED RAT IS ASSOCIATED WITH INCREASED mRNA EXPRESSION OF LIVER γ‐BBH AND KIDNEY OCTN2

Endurance training alters the oxidative capacity of tissues to favor the oxidation of fatty acids. In response to training, carnitine concentrations in plasma are increased suggesting that either carnitine biosynthesis is stimulated or renal uptake of carnitine from the urine is enhanced, or both. Carnitine is essential in the oxidation of fatty acids by permitting their transport into the mitochondria for oxidation. Carnitine is released into the circulation following its hydroxylation by γ‐butyrobetaine hydroxylase (BBH), the final enzyme in the biosynthetic pathway in liver. The organic cation transporter (OCTN2) is also important in the distribution of carnitine by facilitating renal reabsorption of carnitine from the urine. To investigate whether these proteins are implicated in carnitine homeostasis in response to exercise, BBH and OCTN2 expression were determined following 10 weeks of treadmill exercise training in male Wistar rats. Exercise training significantly increased the level of total carnitine in plasma, whereas in liver the level of total carnitine (sum of free, short‐chain acylcarnitine and long‐chain acylcarnitine) was not modified by exercise. In exercise‐trained rats, BBH expression in liver was significantly increased compared to sedentary rats, whereas in kidney a significant decrease was observed. OCNT2 expression in both liver and kidney were significant increased in exercise‐trained rats. Our results indicate that the improved plasma carnitine status in the trained rat can be explained, in part, by increases in both carnitine biosynthesis and renal reabsorption of carnitine.

Long-Term Exercise Training Attenuates Age-Related Diastolic Dysfunction: Association of Myocardial Collagen Cross-Linking

The incidence of diastolic heart failure increases dramatically with age. We investigated the impact of long-term exercise training on age-related diastolic dysfunction. Old (25-month-old) male Fischer 344 rats were studied after 12 weeks of treadmill exercise training or sedentary cage life (N=7, in each group). We determined cardiac performance using a pressure-volume conductance catheter and magnetic resonance imaging. Collagen volume fraction (CVF) and myocardial collagen solubility by pepsin as an index of advanced glycation end products (AGEs) cross-linked collagen were measured. The maximal slope of systolic pressure increment (+dP/dt) and the slope of end-systolic pressure-volume relation were higher, and end diastolic volume (EDV), ΔEDV (the percentage of the EDV increment-to-baseline EDV) and the slope of end-diastolic pressure-volume relation were lower in training group. The maximal slope of diastolic pressure decrement (-dP/dt) and time constant of LV pressure decay (τ) had no difference. AGEs cross-linked collagen, not CVF was reduced by exercise training. Long-term exercise training appears to attenuate age-related deterioration in cardiac systolic function and myocardial stiffness and could be reduce in pathologic AGEs cross-linked collagen in myocardium.

Exercise training in late middle‐aged male Fischer 344 × Brown Norway F1‐hybrid rats improves skeletal muscle aerobic function

The Fischer 344 x Brown Norway F1-hybrid (F344BN) rat has become an increasingly popular and useful strain for studying age-related declines in skeletal muscle function because this strain lives long enough to experience significant declines in muscle mass. Since exercise is often considered a mechanism to combat age-related declines in muscle function, determining the utility of this strain of rat for studying the effects of exercise on the ageing process is necessary. The purpose of this study was to evaluate the plasticity of skeletal muscle aerobic function in late middle-aged male rats following 7 weeks of treadmill exercise training. Training consisted of 60 min per day, 5 days per week with velocity gradually increasing over the training period according to the capabilities of individual rats. The final 3 weeks involved 2 min high-intensity intervals to increase the training stimulus. We used in situ skeletal muscle aerobic metabolic responses and in vitro assessment of muscle mitochondrial oxidative capacity to describe the adaptations of aerobic function from the training. Training increased running endurance from 11.3 +/- 0.6 to 15.5 +/- 0.8 min, an improvement of approximately 60%. Similarly, distal hindlimb muscles from trained rats exhibited a higher maximal oxygen consumption in situ (23.2 +/- 1.3 versus 19.7 +/- 0.8 mumol min(-1) for trained versus sedentary rats, respectively) and greater citrate synthase and complex IV enzyme activities in gastrocnemius (29 and 19%, respectively) and plantaris muscles (24 and 28%, respectively) compared with age-matched sedentary control animals. Our results demonstrate that skeletal muscles from late middle-aged rats adapt to treadmill exercise by improving skeletal muscle aerobic function and mitochondrial enzyme activities. This rat strain seems suitable for further investigations using exercise as an intervention to combat ageing-related declines of skeletal muscle aerobic function.