Protective Effects Of Exercise Training Research Articles

Aerobic Exercise Attenuates Pressure Overload-Induced Myocardial Remodeling and Myocardial Inflammation via Upregulating miR-574-3p in Mice.

Exercise training can promote cardiac rehabilitation, thereby reducing cardiovascular disease mortality and hospitalization rates. MicroRNAs (miRs) are closely related to heart disease, among which miR-574-3p plays an important role in myocardial remodeling, but its role in exercise-mediated cardioprotection is still unclear. A mouse myocardial hypertrophy model was established by transverse aortic coarctation, and a 4-week swimming exercise training was performed 1 week after the operation. After swimming training, echocardiography was used to evaluate cardiac function in mice, and histopathologic staining was used to detect cardiac hypertrophy, myocardial fibrosis, and cardiac inflammation. Quantitative real-time polymerase chain reaction was used to detect the expression levels of miR-574-3p and cardiac hypertrophy markers. Western blotting detected the IL-6 (interleukin-6)/JAK/STAT inflammatory signaling pathway. Echocardiography and histochemical staining found that aerobic exercise significantly improved pressure overload-induced myocardial hypertrophy (n=6), myocardial interstitial fibrosis (n=6), and cardiac inflammation (n=6). Quantitative real-time polymerase chain reaction detection showed that aerobic exercise upregulated the expression level of miR-574-3p (n=6). After specific knockdown of miR-574-3p in mouse hearts with adeno-associated virus 9 using cardiac troponin T promoter, we found that the protective effect of exercise training on the heart was significantly reversed. Echocardiography and histopathologic staining showed that inhibiting the expression of miR-574-3p could partially block the effects of aerobic exercise on cardiac function (n=6), cardiomyocyte cross-sectional area (n=6), and myocardial fibrosis (n=6). Western blotting and immunohistochemical staining showed that the inhibitory effects of aerobic exercise on the IL-6/JAK/STAT pathway and cardiac inflammation were partially abolished after miR-574-3p knockdown. Furthermore, we also found that miR-574-3p exerts cardioprotective effects in cardiomyocytes by targeting IL-6 (n=3). Aerobic exercise protects cardiac hypertrophy and inflammation induced by pressure overload by upregulating miR-574-3p and inhibiting the IL-6/JAK/STAT pathway.

Exercise Training Attenuates Acute β-Adrenergic Receptor Activation-Induced Cardiac Inflammation via the Activation of AMP-Activated Protein Kinase.

Exercise has proven cardiac benefits, but the underlying mechanisms of exercise that protect the heart from acute sympathetic stress injuries remain unknown. In this study, adult C57BL/6J mice and their AMP-activated protein kinase α2 knockout (AMPKα2-/-) littermates were either subjected to 6 weeks of exercise training or housed under sedentary conditions and then treated with or without a single subcutaneous injection of the β-adrenergic receptor (β-AR) agonist isoprenaline (ISO). We investigated the differences in the protective effects of exercise training on ISO-induced cardiac inflammation in wild-type (WT) and AMPKα2-/- mice using histology, enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. The results indicated that exercise training alleviated ISO-induced cardiac macrophage infiltration, chemokines and the expression of proinflammatory cytokines in wild-type mice. A mechanism study showed that exercise training attenuated the ISO-induced production of reactive oxygen species (ROS) and the activation of NLR Family, pyrin domain-containing 3 (NLRP3) inflammasomes. In cardiomyocytes, the ISO-induced effects on these processes were inhibited by AMP-activated protein kinase (AMPK) activator (metformin) pretreatment and reversed by the AMPK inhibitor (compound C). AMPKα2-/- mice showed more extensive cardiac inflammation following ISO exposure than their wild-type littermates. These results indicated that exercise training could attenuate ISO-induced cardiac inflammation by inhibiting the ROS-NLRP3 inflammasome pathway in an AMPK-dependent manner. Our findings suggested the identification of a novel mechanism for the cardioprotective effects of exercise.

Interaction of exercise training with taurine attenuates infarct size and cardiac dysfunction via Akt-Foxo3a-Caspase-8 signaling pathway.

This research aimed to investigate the synergistic protective effect of exercise training and taurine on Akt-Foxo3a-Caspase-8 signaling related to infarct size and cardiac dysfunction. Therefore, 25 male Wistar rats with MI were divided into five groups: sham (Sh), control-MI(C-MI), exercise training-MI(Exe-MI), taurine supplementation-MI(Supp-MI), and exercise training + taurine-MI(Exe + Supp-MI). The taurine groups were given a 200mg/kg/day dose of taurine by drinking water. Exercise training was conducted for 8weeks (5days/week), each session alternated 2min with 25-30% VO2peak and 4min with 55-60% VO2peak for 10 alternations. Then, the left ventricle tissue samples were taken from all groups. Exercise training and taurine activated Akt and decreased Foxo3a. Expression of the caspase-8 gene was increased in cardiac necrosis after MI, While, after 12weeks of intervention decreased. Results exhibited that exercise training combined with taurine has a greater effect than either alone on activating the Akt-Foxo3a-caspase signaling pathway (P < 0.001). MI-induced myocardial injury leads to increase collagen deposition (P < 0.001) and infarct size and results in cardiac dysfunction via reduced stroke volume, ejection fraction, and fractional shortening (P < 0.001). Exercise training and taurine improved cardiac functional parameters (SV, EF, FS) and infarct size (P < 0.001) after 8weeks of intervention in rats with MI. Also, the interaction of exercise training and taurine has a greater effect than alone on these variables. Interaction of exercise training with taurine supplementation induces a general amelioration of the cardiac histopathological profiles and improves cardiac remodeling via activating Akt-Foxo3a-Caspase-8 signaling with protective effects against MI.

Exercise training attenuates angiotensin II-induced cardiac fibrosis by reducing POU2F1 expression

BackgroundExercise training protects against heart failure. However, the mechanism underlying the protective effect of exercise training on angiotensin II (Ang II)-induced cardiac fibrosis remains unclear. MethodsAn exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used. Ang II (1.44 mg/kg/day) was administered to induce cardiac fibrosis. RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis. Primary adult mouse cardiac fibroblasts (CFs) were used in vitro. Adeno-associated virus serotype 9 was used to overexpress POU domain, class 2, transcription factor 1 (POU2F1) in vivo. ResultsExercise training attenuated Ang II-induced cardiac fibrosis and reversed 39 gene expression changes. The transcription factor regulating the largest number of these genes was POU2F1. Compared to controls, POU2F1 was shown to be significantly upregulated by Ang II, which is itself reduced by exercise training. In vivo, POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis. In CFs, POU2F1 promoted cardiac fibrosis. CCAAT enhancer-binding protein β (C/EBPβ) was predicted to be the transcription factor of POU2F1 and verified using a dual-luciferase reporter assay. In vivo, exercise training activated AMP-activated protein kinase (AMPK) and alleviated the increase in C/EBPβ induced by Ang II. In CFs, AMPK agonist inhibited the increase in C/EBPβ and POU2F1 induced by Ang II, whereas AMPK inhibitor reversed this effect. ConclusionExercise training attenuates Ang II-induced cardiac fibrosis by reducing POU2F1. Exercise training inhibits POU2F1 by activating AMPK, which is followed by the downregulation of C/EBPβ, the transcription factor of POU2F1.

Inhibition of Rho/ROCK signaling pathway participates in the cardiac protection of exercise training in spontaneously hypertensive rats

Exercise training (ExT) is capable of improving the heart function of spontaneously hypertensive rats (SHRs), but the underlying molecular mechanisms remain elusive. This study was aimed to investigate whether inhibition of RhoA/ROCK signaling pathway contributes to the cardiac protection by low-intensity ExT in SHRs. The results demonstrated that, compared with Wistar-Kyoto (WKY) rats, SHRs obviously exhibited higher blood pressure, increased heart weight index and thickness of left ventricular wall, decreased left ventricular function, damaged myocardial construction, and increased collagen fiber of left ventricle (P < 0.05 or P < 0.01). Meanwhile, the mRNA and protein expression levels of RhoA and ROCK in the heart of SHRs were significantly increased, compared with those of WKY rats (P < 0.05 or P < 0.01). Interestingly, the pathological changes of heart aforementioned were all improved in SHR-ExT rats compared with SHR-Sed rats (P < 0.05 or P < 0.01), indicating the cardiac protection of exercise training. In addition, the cardiac protective effect of exercise training could be blocked by LPA, an activator of Rho/ROCK signaling, and the protective effect in SHR rats could be mimicked by Fasudil, an inhibitor of Rho/ROCK signaling. The results strongly suggest that low-intensity ExT can protect heart against structure and function through inhibiting Rho/ROCK signaling pathway in hypertensive rats.

Exercise Training Ameliorates Renal Oxidative Stress in Rats with Chronic Renal Failure.

In patients with chronic kidney disease, exercise training with moderate intensity protects renal function and improves mortality. However, the mechanisms of the renal protective effects of exercise training in chronic kidney disease have not been clarified. This study investigated the effects of exercise training on renal NADPH oxidative and xanthine oxidase, which are major sources of reactive oxygen species, in rats with chronic renal failure. Six-week-old, male Sprague–Dawley rats were divided into the sham operation, 5/6 nephrectomy (Nx)+ sedentary, and Nx+ exercise training groups. The Nx+ exercise training group underwent treadmill running. After 12 weeks, systolic blood pressure, renal function, malondialdehyde, renal NADPH oxidase, and xanthine oxidase were examined. Nx induced hypertension, proteinuria, and renal dysfunction, and exercise training attenuated these disorders. Although the plasma levels of malondialdehyde were not different among the group, urinary levels were increased by Nx and decreased by exercise training. Renal activity and expression of NADPH oxidase and xanthine oxidase were increased by Nx and decreased by exercise training. These results indicate that exercise training attenuates hypertension and renal dysfunction and ameliorates NADPH oxidase and xanthine oxidase in rats with chronic renal failure, suggesting that the reduction of reactive oxygen species generation may be involved in the renal protective effects of exercise training.

Gut microbiome mediates the protective effects of exercise after myocardial infarction

BackgroundGut microbiota plays important roles in health maintenance and diseases. Physical exercise has been demonstrated to be able to modulate gut microbiota. However, the potential role of gut microbiome in exercise protection to myocardial infarction (MI) remains unclear.ResultsHere, we discovered exercise training ameliorated cardiac dysfunction and changed gut microbial richness and community structure post-MI. Moreover, gut microbiota pre-depletion abolished the protective effects of exercise training in MI mice. Furthermore, mice receiving microbiota transplants from exercised MI mice had better cardiac function compared to mice receiving microbiota transplants from non-exercised MI mice. Mechanistically, we analyzed metabolomics in fecal samples from exercised mice post-MI and identified 3-Hydroxyphenylacetic acid (3-HPA) and 4-Hydroxybenzoic acid (4-HBA), which could be applied individually to protect cardiac dysfunction post-MI and apoptosis through NRF2.ConclusionsTogether, our study provides new insights into the role of gut microbiome in exercise protection to MI, offers opportunities to modulate cardiovascular diseases by exercise, microbiome and gut microbiota-derived 3-HPA and 4-HBA.2VpFEiBoi5zKv8qdp_bZN4Video

Exercise Training Alleviates Alzheimer’s Disease‐Associated Aortic Endothelial Dysfunction

BackgroundsA strong association between cardiovascular disease and Alzheimer’s disease (AD) has been reported, but its possible mechanism has been unknown. We have tested whether aortic endothelial function in AD is impaired and investigated the protective effect of exercise training (EX) on endothelial function in aorta of AD mice.METHODSWild type (C57BL/6, WT) and AD (APP/PS1dE9, AD) mice underwent treadmill training (WT‐EX and AD‐EX) or remained sedentary for 12 weeks. The expression of total‐and phosphorylated‐endothelial nitric oxide synthase (t‐eNOS and p‐eNOS), beta‐amyloid, and superoxide dismutase 2 (SOD2) were quantified by Western blot analysis.RESULTSt‐eNOS and p‐eNOS expressions in AD were decreased compared to WT but EX increased both t‐eNOS and p‐eNOS in AD (P &lt; 0.01 and P = 0.09). Beta‐amyloid levels in AD were higher compared to WT but EX decreased it (P &lt; 0.05). SOD2 levels in AD were increased by EX (P &lt; 0.05) whereas there was no change in WT.CONCLUSIONRegular aerobic exercise alleviates e‐NOS‐mediated endothelial dysfunction in aorta of AD mice possibly via reduced beta‐amyloid and increased SOD2 levels.

Perfusion of Brain Preautonomic Areas in Hypertension: Compensatory Absence of Capillary Rarefaction and Protective Effects of Exercise Training.

Remodeling of capillary rarefaction and deleterious arteries are characteristic hallmarks of hypertension that are partially corrected by exercise training. In addition, experimental evidence showed capillary rarefaction within the brain cortex and reduced cerebral blood flow. There is no information on hypertension- and exercise-induced effects on capillary profile and function within preautonomic nuclei. We sought now to evaluate the effects of hypertension and exercise training (T) on the capillary network within hypothalamic paraventricular (PVN) and solitary tract (NTS) nuclei, and on the remodeling of brain arteries. Age-matched spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY), submitted to moderate T or kept sedentary (S) for three months, were chronically cannulated for hemodynamic recordings at rest. Rats were anesthetized for i.v. administration of fluorescein isothiocyanate (FITC)-dextran (capillary volume/density measurements) or 4% paraformaldehyde perfusion (basilar, middle, and posterior arteries' morphometry) followed by brain harvesting and processing. Other groups of conscious rats had carotid blood flow (CBF, ultrasound flowmeter) acquired simultaneously with hemodynamic recordings at rest and exercise. SHR-S exhibited elevated pressure and heart rate, reduced CBF, increased wall/lumen ratio of arteries, but no capillary rarefaction within the PVN and NTS. T improved performance gain and caused resting bradycardia in both groups; reduction of pressure and sympathetic vasomotor activity and normalization of the wall/lumen ratio were only observed in SHR-T. T groups responded with marked PVN and NTS capillary angiogenesis and augmented CBF during exercise; to avoid overperfusion at rest, reduced basal CBF was observed only in WKY-T. Data indicated that the absence of SHR-S capillary rarefaction and the intense SHR-T angiogenesis within autonomic areas associated with correction of deleterious arteries' remodeling are essential adjustments to hypertension and exercise training, respectively. These adaptive responses maintain adequate baseline perfusion in SHR-S and SHR-T preautonomic nuclei, augmenting it in exercised rats when a well-coordinated autonomic control is required.

Exercise Training Protects Against Heart Failure Via Expansion of Myeloid-Derived Suppressor Cells Through Regulating IL-10/STAT3/S100A9 Pathway.

Exercise training (ET) has a protective effect on the progression of heart failure, however, the specific mechanism has not been fully explored. Myeloid-derived suppressor cells (MDSCs) are a group of myeloid-derived immunosuppressive cells, which showed a protective effect in the progression of heart failure. Thus, we hypothesized that the protective effect of ET on heart failure may be related to the infiltration of MDSCs. C57BL/6 mice were made to run on a treadmill 6× a week for 4 weeks followed by isoproterenol injection from third week. Heart function was evaluated by echocardiography and the proportion of MDSCs was detected by flow cytometry. Hypertrophic markers, cardiac fibrosis, and inflammatory factors were detected by real-time PCR, ELISA, histological staining, and Western blot. ET treatment in isoproterenol-induced heart failure mice (n=7) enhanced cardiac function (57% increase in FS%, P=0.002) and improved morphological changes compared with isoproterenol mice (n=17). ET further caused 79% increasing in cardiac MDSCs in isoproterenol mice (P<0.001). In addition, depletion of MDSCs by 5-Fluorouracil blunted the cardio-protective effect of ET. T-cell proliferation assay showed that ET did not affect the suppressive activity of MDSCs. Furthermore, we found that ET activated the secretion of IL (interleukin)-10 by macrophages in isoproterenol mice. MDSCs expansion and cardio protection was not present in tamoxifen-inducible macrophage-specific IL-10 knockout mice. Western blot results confirmed that IL-10 regulated the differentiation of MDSCs through the translocation of p-STAT3 (signal transducer and activator of transcription 3)/S100A9 (S100 calcium-binding protein A9) to the nucleus. ET could increase MDSCs by stimulating the secretion of IL-10 from macrophage, which was through IL-10/STAT3/S100A9 signaling pathway, thereby achieving the role of heart protection.

EXERCISE TRAINING PROTECTED CARDIAC DAMAGE FROM DOXORUBICIN-INDUCED HEART FAILURE IN SPRAGUE-DAWLEY RATS

Objective: Heart failure is a complex end stage result of various cardiovascular diseases, and has a poor prognosis. Exercise training according to oxidative stress, myocardial fibrosis, inflammation pathways improve cardiac function. The aim of this study was to investigate the possible protective effects of exercise training against cardiac damage in doxorubicin (DOX)-induced heart failure in Sprague-Dawley Rats. Design and method: This study used 45 male Sprague-Dawley (SD) rats weighing 150 ± 20 g that were randomly divided into a control group (normal saline), doxorubicin (DOX) group and DOX plus exercise (DOX + E) group. Heart failure was induced experimentally by intraperitoneal injections of the cardiotoxic agent DOX. All groups received different treatment for 8 weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes; the blood samples were stored at minus 80°C until use. Heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The heart was stored in liquid nitrogen for immunoblotting or mRNA analysis. Results: Left ventricular fractional shortening and ejection fraction were higher in DOX + E group rats than in DOX group rats on an echocardiographic examination (Figure 1 and Table 1). Significant cardiac tissue damage (haematoxylin and eosin, Masson's trichrome staining) was seen in rats of the DOX group compared to those of the DOX + E group (Figure2). Exercise inhibited DOX-induced cardiac fibrosis (transforming growth factor, smooth muscle actin, collagen I, and collagen III) and oxidative stress (Nox4, p53) in an immunoblotting analysis (Figure 3 and 4). Conclusions: These results indicate that exercise training may be a potential therapeutic target for cardiac damage caused by DOX-induced heart failure.

Resistance Training Enhances Renal Function in Experimental Renal Ischemia-Reperfusion

Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is among the most common complications in hospitalized patients. In recent years, it has been argued that exercise is an approach to attenuate impairments caused by AKI. The purpose of this study was to investigate whether eight weeks of resistance training (RT) has protective effects on IRI. Thirty male Wistar rats (210-230 g) were randomly divided into four groups, including RT+ISC (n=7), RT (n=8), ISC (n=7), and sham (n=8). Animals underwent eight weeks of RT, and 48 hours after the last training session, ischemia (45 min) reperfusion (24 h) was induced. Then animals were sacrificed, and blood and kidney tissue samples were collected to measure creatinine (Cr), blood urea nitrogen (BUN), kidney tissue damage score (KTDS), and kidney weight (KW). The results showed that IRI caused a significant increase in Cr, BUN, KTDS, and KW (p-value &lt;0.05), while RT decreased the severity of KTDS, Cr, and BUN remarkably. (p≤0.05). RT, however, did not attenuate KW (p≤0.05). Overall, the findings of our study provide evidence that RT can attenuate IRI-induced AKI considering enhanced biomarkers; However, further research should be conducted to make certain about the protective effects of exercise training, especially RT.

Effects of exercise training on renal interstitial fibrosis and renin-angiotensin system in rats with chronic renal failure.

To clarify the mechanisms of the renal protective effects of exercise training, we examined the effects of exercise training on the renal interstitial fibrosis and renin-angiotensin system (RAS) in rats with chronic renal failure. Six-week-old male Sprague-Dawley rats were divided into three groups: sham operation; 5/6 nephrectomy + sedentary; 5/6 nephrectomy + exercise training. The 5/6 nephrectomy + exercise training group underwent treadmill running (20 m/min, 60 min/day, 5 days/week). After 12 weeks, renal function, histology and protein expression of collagen type I, transforming growth factor-β1 (TGF-β1), matrix metalloproteinase (MMP), tissue inhibitors of metalloproteinase (TIMP) and RAS components in the renal cortex were examined. Exercise training ameliorated the 5/6 nephrectomy-induced hypertension, proteinuria, renal dysfunction, glomerular sclerosis and renal interstitial fibrosis. 5/6 Nephrectomy increased the expression of collagen type I, TGF-β1, MMP-2, MMP-9, TIMP-1, angiotensinogen, angiotensin-converting enzyme (ACE), (pro)renin receptor and angiotensin II type 1 receptor, and exercise training inhibited the 5/6 nephrectomy-increased expression of collagen type I, TGF-β1, TIMP-1, angiotensinogen and ACE expressions. 5/6 Nephrectomy decreased the expression of renin, ACE2, angiotensin II type 2 receptor and Mas receptor, and exercise training inhibited the 5/6 nephrectomy-decreased expressions. These results indicated that exercise training attenuates the progression of glomerular sclerosis and renal interstitial fibrosis in chronic renal failure rats. The renal protective effects of exercise training may be mediated by ameliorating the renal collagen turnover and the exacerbation of renal RAS.

Oxidative Stress and Inflammation Induced by Waterpipe Tobacco Smoking Despite Possible Protective Effects of Exercise Training: A Review of the Literature.

The prevalence of waterpipe tobacco smoking (WTS), which is also known as ghalyan, shisha or hookah, is increasing rapidly around the world, especially among youth. Growing interest in this form of tobacco smoking can be traced, in part, to the use of flavored tobacco products, social acceptability as a safer option than cigarettes, and its consideration as a relaxation method or entertainment. However, there is a well-established association between WTS and oxidative stress that causes irreversible chronic pathological conditions such as cardiovascular and respiratory problems, as well as different types of cancers, and thus increases the risk of mortality. Clearly, induction of inflammation status through increased reactive oxygen species (ROS), which in turn leads to oxidative stress and harm to lipids, DNA, and proteins, is the most plausible mechanism to explain the potential harmful effects of WTS. Unlike WTS, well-designed exercise training programs increase ROS to the extent that it is beneficial to the body. In this study, we aimed to review available evidence on the impact of exercise training on oxidative stress and inflammation status. We also summarize the effect of acute and chronic WTS on different exercise capacities.

EXERCISE TRAINING AMELIORATES CEREBROVASCULAR DYSFUNCTION IN ALZHEIMER'S DISEASE; A ROLE OF P2Y2 RECEPTOR AND ENDOPLASMIC RETICULUM STRESS

PURPOSE: To determine the protective effect of exercise training on P2Y2 receptor-mediated and ER stress-associated cerebrovascular dysfunction in AD. METHODS: We used the control mice (CON; C57BL/6), CON with exercise training (CON+EX), AD mice (AD; APP/PS1) and AD with EX (AD+EX). At 7 to 9 months of age, CON+EX and AD+EX mice underwent 10-12 weeks of aerobic exercise training on the treadmill, running for an hour at 15m/min at a 5% grade for 5 days a week. To test the purinergic receptor-dependent vasoreactivity, a posterior cerebral artery (PCA) was isolated and pressurized, and then ATP (2-MeS-ATP, 1 nmol/L to 10 μmol/L)-induced dose-dependent vasoreactivities were determined at 10-12 months of age. Human brain micro endothelial cells (HBMECs) were exposed to laminar shear stress (LSS) at 20 dyne/cm2 for 30 mins, 2 hrs, and 24 hrs. Western blotting was utilized to analyze the expression of P2Y2 receptors, endothelial nitric oxide synthesis (eNOS), and ER stress signaling to define the effect of exercise training on cerebrovascular dysfunction. RESULTS: ATP-induced vasodilation in PCA from CON mice, but it caused vasoconstriction in PCA from AD mice. Notably, exercise training reversed ATP-induced vasoconstriction in PCA from AD mice to vasodilation (AD+EX) comparable to CON mice. Exercise training reduced the elevation of APP expression and increased P2Y2 receptor and Akt/eNOS expression in AD mice brain. Also, LSS increased the expression of P2Y2 receptor and eNOS in HBMECS, but these increases were blunted by P2Y2 receptor inhibitor (AR-C) in HBMECs. Exercise training normalized the abnormal expression of ER stress markers; p-IRE1, p/t-eIF2α, CHOP, and ER stress-associated apoptosis; Bax and Bcl-2 in AD mice brain. CONCLUSION: Exercise training improves the cerebrovascular dysfunction in AD possibly through P2Y2 receptor-and ER stress-dependent endothelial dysfunction.

Epinephrine Responsiveness is Reduced in Livers from Trained Mice

Catecholamines increase liver glucose production at least in part through increases in glycogenolysis and gluconeogenesis. To date, the effects of prior exercise training on the liver’s response to epinephrine, in vivo, have not been fully elucidated. To examine the role of epinephrine signaling on indices of liver glucose production in trained mice, male C57BL/6 mice were subject to either 12 days of voluntary wheel running (TR) or remained sedentary (SED). Epinephrine (0.5 mg/kg body weight), or vehicle were injected intraperitoneally following 12 days of training and tissues harvested 15 minutes post‐injection. The rise in blood glucose following epinephrine injection was significantly blunted in trained compared to sedentary mice and this was paralleled by a blunted reduction in liver glycogen in trained mice. There was a main effect of epinephrine to increase the phosphorylation of protein kinase‐A substrates (pPKAs), which was driven by increases in the sedentary, but not trained, mice. Similarly, epinephrine‐induced increases in the mRNA expression of α‐ and β‐adrenergic receptor 1 and 2 and glucose‐6‐phosphatase were greater in SED compared to TR mice. Exercise and epinephrine decreased serum insulin levels and increased glucagon levels, however, there were no differences within epinephrine treated groups. Changes in phosphorylated AKT, AMPK, and phosphodiesterase 4B protein content, negative regulators of PKA signaling, do not explain the protective effects of exercise training against epinephrine induced increases in blood glucose and liver glycogen breakdown. Taken together our data suggest that prior exercise training reduces the liver’s response to epinephrine. This could be beneficial in the context of training‐induced sparing of glycogen during exercise.Support or Funding InformationThis work was funded, in part, through a National Sciences and Engineering Research Council of Canada (NSERC) grant to D.C.W., who is a Tier II Canada Research Chair in Lipids, Metabolism, and Health. H.A.D was supported by an Ontario Graduate Scholarship. G.L.M. was supported by an Ontario Graduate Scholarship and subsequently an NSERC Canada Graduate Scholarship. L.K.T. was supported by a Dairy Farmers of Ontario Doctoral Research Assistantship and an NSERC Postgraduate Scholarship.

Effects of Treadmill Running on Oxidative Stress and Heat Shock Protein in Early Stage of 3xTg-AD Mice

PURPOSE The mechanisms underlying the protective effects of exercise training against cognitive decline are not fully understood. This study aimed to investigate the effects of treadmill running on oxidative stress and heat shock protein levels in a mouse model of early stage triple transgenic Alzheimer’s disease (3xTg-AD). METHODS We divided 5-month old 3xTg-AD mice (N=20) into the control (AD+CON, n=10) and exercise training (AD+EX, n=10) groups. Background strain mice were included as wild-type controls (WT, n=10). AD+EX mice were subjected to treadmill running at a speed of 15 m/min, 50 min/day, 5 days/week for 12 weeks. RESULTS Treadmill running protected 3xTg-AD mice from cognitive decline and significantly suppressed the increase in soluble Aβ1-42 protein levels (AD+CON vs AD+EX, p=0.015) and the progression of oxidative damage. This was evidenced by significant increase in anti-oxidative protein levels such as superoxide dismutase-1 (SOD-1), heme oxygenase (HO-1) and heat shock protein 70 (HSP70) in the hippocampus of AD+EX mice compared to AD+CON mice. Moreover, the brain-derived neurotrophic factor (BDNF) and synaptic proteins such as PSD95 and synaptophysin were upregulated in AD+EX mice compared to AD+CON mice. CONCLUSIONS Our findings support and extend previous studies reporting the preventive effects of exercise training on the pathological processes of the Alzheimer’s disease in the 3xTg AD mouse model. 색인어: ì•Œì¸ í•˜ì´ë¨¸ 병, íŠ¸ë ˆë“œë°€ 운동, 산화성 ìŠ¤íŠ¸ë ˆìŠ¤, 열쇼크 단백질, 3xTg-AD Keywords: Alzheimer’s disease, treadmill running, oxidative stress, heat shock protein, 3xTg-AD

Protective effect of exercise training against the progression of Alzheimer’s disease in 3xTg-AD mice

Mechanisms underlying the protective effect of exercise training against the progression of Alzheimer’s disease (AD) are not fully understood. This study investigated the effects of treadmill running on Aβ plaque burden and hyper-phosphorylated tau protein, neuro-inflammation, mitochondrial dysfunction, and adult neurogenesis markers in conjunction with cognitive impairments in triple transgenic AD (3xTg-AD) mice. At age of three months, the 3xTg-AD mice were assigned to control (AD, n = 10) or exercise training (AD-EXE, n = 10). The AD-EXE mice were trained on a rodent motor-driven treadmill with a frequency of 5 days per week for 12 weeks. As a consequence, AD-EXE mice had lower levels of Aβ plaque burden and neuro-inflammation, positive changes in mitochondrial function toward a more robust phenotype, and increases in hippocampal adult neurogenesis markers in the hippocampus and cerebral cortex compared to AD mice. The alleviating effects of treadmill running against the progression of the disease were accompanied by enhanced AD-like cognitive performances based on Morris water maze. The current findings support and extend previous studies reporting the protective effect of physical exercise against the progression of the disease in AD animal models.

The effect of exercise on purinergic receptor‐mediated cerebrovascular dysfunction in Alzheimer's disease

IntroductionCerebrovascular dysfunction is a critical initial step of Alzheimer's disease (AD). Adenosine triphosphate (ATP) regulates cerebral blood flow through purinergic receptors. The aim of this study is to investigate the protective effect of exercise training on ATP‐induced purinergic receptor‐mediated cerebrovascular dysfunction in the AD and its underlying mechanisms.MethodsWe used the control mice (CON; C57BL/6), CON with exercise training (CON‐EX), AD mice (AD; APP/PS1) and AD with EX (AD‐EX). At 7 to 9 months of age, CON‐EX and AD‐EX mice underwent 10–12 weeks of aerobic exercise training, which consisted of 1 hour of treadmill running at 15m/min at a 5% grade. To test the purinergic receptor‐dependent vasoreactivity, a posterior cerebral artery (PCA) was isolated and ATP (2‐MeS‐ATP, 1 nmol/L to 10 μmol/L)‐induced dose‐dependent vascular dilation/constriction response was determined at 10–12 months of age. Western blotting was utilized to analyze the expression of P2Y2 receptors (P2Y2R), total eNOS (t‐eNOS) and phosphorylated eNOS (p‐eNOS) in the brain.ResultsATP induced vasodilation of PCA in CON and CON+EX mice, but it induced vasoconstriction in AD mice. Notably, exercise training reverses ATP‐induced vasoconstriction in the AD to vasodilation (AD+EX) comparable to CON mice. Western blotting data demonstrated that P2Y2R and p‐eNOS expression were significantly diminished in AD mice compared to CON mice, but they were elevated in AD‐EX mice brain. There was no significant difference in t‐eNOS expression among mice groups.ConclusionOur findings suggest that ATP‐induced purinergic receptor‐dependent cerebrovascular function is impaired in the AD. However, exercise training reverses ATP‐induced purinergic receptor‐dependent vasoconstriction to vasodilation mainly through the alteration of P2Y2R and p‐eNOS expression in the AD‐EX.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Protective effects of exercise training on endothelial dysfunction induced by total sleep deprivation in healthy subjects

Protective effects of exercise training on endothelial dysfunction induced by total sleep deprivation in healthy subjects