Exercise-trained Rats Research Articles

Remedial role of exercise training to deep-fried oil-induced metabolic and histological changes in Wistar rats.

Exercise training is a well-known lifestyle to maintain good health. The present study was conducted to explore the effect of regular exercise training (for 15min) on biochemical, physiological, and histological changes in fried oil intake (5g/kg body weight, for 5weeks) with or without raw oil supplementation. Liver disease and heart muscle injury were accounted for by significant (p<.05) increase in liver and heart biomarker enzymes in serum. Creatinine and urea level were also significantly increased in the fried oil-fed group as a sign of kidney injury. But all the biological markers including triglycerides, low-density lipoprotein cholesterol (LDL-C) was decreased significantly (p<.05) in the exercise-trained rat group. These metabolic changes were substantiated by the histological study of respective organs. Therefore, people should avoid repeatedly deep-fried oil consumption rather than fresh ones though regular exercise training has been found to resolve these metabolic abnormalities. PRACTICAL APPLICATIONS: Exercise training is a common practice to reduce the onset of some metabolic abnormalities for example cardiovascular disease, non-alcoholic fatty liver disease, chronic kidney disease, and also prevents various cell and tissue damages. Repeated frying of vegetable oil not only reduces its nutritional value but also produce free fatty acids and other toxic compounds. The present study revealed that repeatedly heated vegetable oil consumption causes injuries in the heart, liver, kidney, and small intestine by the oxidative products. As a result, the level of biomarkers of these responsive organs was found to be elevated. But regular exercise training ameliorated these detrimental effects. So, in terms of public health concern, regular exercise is one of the best ways to keep the body fit especially those who are consuming deep-fried oil.

Pterostilbene Enhances Endurance Capacity via Promoting Skeletal Muscle Adaptations to Exercise Training in Rats.

It has been demonstrated that skeletal muscle adaptions, including muscle fibers transition, angiogenesis, and mitochondrial biogenesis are involved in the regular exercise-induced improvement of endurance capacity and metabolic status. Herein, we investigated the effects of pterostilbene (PST) supplementation on skeletal muscle adaptations to exercise training in rats. Six-week-old male Sprague Dawley rats were randomly divided into a sedentary control group (Sed), an exercise training group (Ex), and exercise training combined with 50 mg/kg PST (Ex + PST) treatment group. After 4 weeks of intervention, an exhaustive running test was performed, and muscle fiber type transformation, angiogenesis, and mitochondrial content in the soleus muscle were measured. Additionally, the effects of PST on muscle fiber transformation, paracrine regulation of angiogenesis, and mitochondrial function were tested in vitro using C2C12 myotubes. In vivo study showed that exercise training resulted in significant increases in time-to-exhaustion, the proportion of slow-twitch fibers, muscular angiogenesis, and mitochondrial biogenesis in rats, and these effects induced by exercise training could be augmented by PST supplementation. Moreover, the in vitro study showed that PST treatment remarkably promoted slow-twitch fibers formation, angiogenic factor expression, and mitochondrial function in C2C12 myotubes. Collectively, our results suggest that PST promotes skeletal muscle adaptations to exercise training thereby enhancing the endurance capacity.

Conditional Controlled Light/Dark Cycle Influences Exercise-Induced Benefits in a Rat Model with Osteoarthritis: In Vitro and In Vivo Study

Physical exercise has long been recommended as a treatment for osteoarthritis (OA), though its effects vary based on the exercise protocol. Here, we examined whether environmental lighting conditions influence the anti-inflammatory benefits of exercise in a rat model of OA. Moderate-intensity treadmill exercise (Ex) was performed for six weeks under a 12:12 h light/dark (L/D) cycle, and compared against rats housed in a 24 h continuous light (L/L) environment. L/L conditions were associated with serological changes shortly after OA induction, which exacerbated the inflammatory microenvironment in the joint. Differentiation capacity was also impaired in bone precursor cells isolated from normal rats maintained under L/L conditions, despite elevated inflammatory responses. Exercise training under L/L conditions led to increased corticosterone levels in the blood, which exacerbated the progression of cartilaginous and synovial lesions. Osteoporotic phenomena were also observed in exercise-trained rats maintained under L/L conditions, along with inflammation-induced catabolism in the gastrocnemius muscle. Aberrant light/dark cycle conditions were also found to be associated with suppression of splenic Cry1 expression in exercise-trained rats, leading to dysregulation of immune responses. Taken together, these data suggest that lighting condition may be an important environmental factor influencing the exercise-induced benefits on OA.

Regular Exercise Training with Lutein/zeaxanthin Isomers Regulates Brain Transcription Factors and Neurotrophic and Synaptic Proteins in Rats (P06-020-19)

ObjectivesLutein/zeaxanthin isomers (L/Zi), the major carotenoids, have demonstrated potent antioxidant and antiinflammation. This study was conducted to clarify the effects of L/Zi on brain transcription and brain-derived neurotrophic factors and synaptic proteins combined with exercise training in rats. MethodsWistar rats (age: 8 wks) were allocated into four groups: (i) Control: no treatments (ii) L/Zi: Rats treated with L/Zi (100 mg L/Zi/kg BW); (iii) Exercise: Rats with regular exercise only, (iv) Exercise + L/Zi: Rats with combined treatment of L/Zi (100 mg L/Zi/kg BW) and regular exercise. The exercise practice was carried out on a motor-driven rodent treadmill at 25 m/min, 45 min/day, 5 d/week for 8 wks. ResultsRats with combined treatment of L/Zi (100 mg L/Zi/kg BW) and regular exercise. The exercise practice was carried out on a motor-driven rodent treadmill at 25 m/min, 45 min/day, 5 d/week for 8 wks. Brain nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and heme oxygenase-1(HO-1) levels increased and nuclear factor (NF-κB) reduced in the combined group. In addition, L/Zi supplementation increased cerebral cortex brain-derived neurotrophic factor (BDNF), synapsin I, synaptophysin (SYP) and growth-associated protein-43 (GAP-43) levels both control and exercised rats (P < 0.001 for all). The highest cerebral cortex BDNF, synapsin I, SYP and GAP-43 levels were detected in the combined group. ConclusionsThese results suggest that regular exercise training with L/Zi may improve brain function by regulating transcription and brain-derived neurotrophic factors and synaptic proteins in rats. Funding SourcesThis study was supported by the Omniactive Health Technologies (NJ, USA) and partially supported by the Turkish Academy of Sciences (Ankara, Turkey).

Exercise training restores the myogenic response in skeletal muscle resistance arteries and corrects peripheral edema in rats with heart failure.

Impairment of the myogenic response can affect capillary hydrostatic pressure and contribute to peripheral edema and exercise intolerance, which are markers of heart failure (HF). The aim of this study was to assess the effects of exercise training (ET) on myogenic response in skeletal muscle resistance arteries and peripheral edema in HF rats, focusing on the potential signaling pathways involved in these adjustments. Male Wistar rats were submitted to either coronary artery occlusion or a sham-operated surgery. After 4 wk, an exercise test was performed, and the rats were divided into the following groups: untrained normal control (UNC) and untrained HF (UHF) and exercise- trained (on treadmill, 50-60% of maximal capacity) NC (TNC) and exercise-trained HF (THF). Caudal tibial artery (CTA) myogenic response was impaired in UHF compared with UNC, and ET restored this response in THF to NC levels and increased it in TNC. Rho kinase (ROCK) inhibitor abolished CTA myogenic response in the untrained and blunted it in exercise-trained groups. CTA-stored calcium (Ca2+) mobilization was higher in exercise-trained rats compared with untrained rats. The paw volume was higher in UHF rats, and ET decreased this response compared with UNC. Myogenic constriction was positively correlated with maximal running distance and negatively correlated with paw volume. The results demonstrate, for the first time, that HF impairs the myogenic response in skeletal muscle arteries, which contributes to peripheral edema in this syndrome. ET restores the myogenic response in skeletal muscle arteries improving Ca2+ sensitization and handling. Additionally, this paradigm also improves peripheral edema and exercise intolerance. NEW & NOTEWORTHY The novel and main finding of the present study is that moderate intensity exercise training restores the impaired myogenic response of skeletal muscle resistance arteries, exercise intolerance and peripheral edema in rats with heart failure. These results also show for the first time to our knowledge that exercise training improving calcium sensitization through the ROCK pathway and enhancing intracellular calcium handling could contribute to restoration of flow autoregulation to skeletal muscle in heart failure.

Effect of Hypoxia on Prostate Cancer Cell Viability in Serum and Prostate Conditioned Media from Mixed‐Intensity Exercise Trained Rats

BackgroundResearch suggests exercise training may alter the tumor microenvironment and facilitate conventional treatment, but the effects of exercise on prostate tumor cell growth characteristics (e.g., viability) are not well understood. In human prostate cancer cells (PC‐3), long time exposure to hypoxia decreases cellular proliferation and migration. However, whether exercise training alters tumor cell viability in hypoxia is unknown. We hypothesized that serum‐supplemented media (SSM) and prostate‐conditioned media (PCM) from mixed‐intensity exercise trained (ET) rats would decease prostate cancer cell viability versus sedentary (SED) rats in hypoxia.MethodsMale Nrf2 rats (10–12 mo old) were randomly placed into an ET (n = 10) and a SED control (n = 4) group. The ET rats ran on a motorized treadmill for 5 days/week for 10–11 weeks. Blood serum and whole prostate were collected for preparation of SSM and PCM, respectively. PC‐3 cancer cells were grown in SSM or PCM from both rat groups for 24–96 h in a 1% O2 custom hypoxia chamber placed within a standard cell incubator. Cell viability was determined using MTT cell proliferation assay.ResultsThere were no significant differences in viable cell number between SED and ET groups at 24 h (0.35 ± 0.03 vs 0.36 ± 0.02 au), 48 h (0.24 ± 0.06 vs 0.29 ± 0.04 au), and 96 h (0.47 ± 0.07 vs 0.52 ± 0.04 au) incubation in PCM. No differences were observed between the SED and ET groups at any time frame when the cells were incubated in SSM.ConclusionOur data does not support an effect of exercise training on cell viability in vitro with exposure to hypoxia. It remains to be determined if the growth supporting environment of the prostate or blood serum are altered with exercise training in vivo.Support or Funding InformationAmerican Cancer Society (RSG‐14‐150‐01‐CCE)NIH (1 R15 HL137156‐01A1)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Exercise-induced β-endorphin release in the anterior cingulate cortex in sedentary and exercise-trained rats

Exercise-induced β-endorphin release in the anterior cingulate cortex in sedentary and exercise-trained rats

Voluntary wheel running prevents the acidosis-induced decrease in skeletal muscle mitochondrial reactive oxygen species emission.

Decreases in pH (acidosis) in vitro can alter skeletal muscle mitochondrial function [respiration and reactive oxygen species (ROS) emission]. However, because skeletal muscles readily adapt to exercise, the effects of acidosis may be different on sedentary vs. trained muscle. The aim of this work was to compare the effects of pH on skeletal muscle mitochondrial function between sedentary vs. exercise-trained male Sprague-Dawley rats ( n = 10 in each cohort). Rates of mitochondrial respiration and ROS emission were determined from the soleus muscle of both cohorts over a physiologic range of pH values (pH 6.2-7.1). Exercise-trained rats had 14% higher mean muscle buffering capacities; 46 and 40% greater enzyme activity of citrate synthase and lactate dehydrogenase, respectively; and greater activity of respiratory complexes I-IV. ADP-stimulated respiration with complex I and II substrates was ∼25% greater in exercise-trained rats but was unaffected by pH in either cohort. In both cohorts, lowering pH decreased respiration only in complex I- and complex II-supported nonphosphorylating (leak) state. However, as pH decreased, ROS emissions in complex I- and complex II-supported leak state decreased only in sedentary rats; in exercise-trained rats, ROS emissions in this state remained constant. We hypothesize that this effect may result from modulation at complex III, which declined 47% per unit pH in sedentary rats, in comparison to 23% in exercise-trained rats. Taken together, these data suggest that pH regulates mitochondrial respiratory complexes and that exercise training can decrease the effects of pH on skeletal muscle mitochondrial function.-Hedges, C. P., Bishop, D. J., Hickey, A. J. R. Voluntary wheel running prevents the acidosis-induced decrease in skeletal muscle mitochondrial reactive oxygen species emission.

Ischemic Preconditioning Efficacy Following Anabolic Steroid Usage: A Clear Difference Between Sedentary and Exercise-Trained Rat Hearts.

Previous studies show that anabolic steroids impair innate cardioprotective mechanisms. Here, we investigated the effect of supraphysiological doses of nandrolone on ischemic preconditioning (IPC) as a potent cardioprotective tool against ischemia reperfusion (IR) injury in rat hearts. Male Wistar rats in two experimental settings of sedentary and exercise-trained (60min/day swimming, 5days/week, for 8weeks) were either pretreated with intramuscular injections of arachis oil (Arach, n = 16) as vehicle or nandrolone decanoate (ND, n = 8), 10mg/kg/week, for 8weeks. At the end, the hearts were excised and perfused in a Langendorff system. Then, the vehicle-treated hearts subdivided into the IR (30min of LAD coronary artery occlusion and 120min reperfusion, n = 8) and IPC (three cycles of 3-min ischemia and 3-min reperfusion before test ischemia, n = 8) groups and nandrolone-treated hearts served as ND + IPC (nandrolone pretreatment before IR and IPC protocols, n = 8) group. Post-ischemic cardiac function and infarct size were assessed. Reperfusion arrhythmias were analyzed using a standard scoring system. In sedentary hearts, ND slightly increased heart-to-body weight ratio and increased baseline cardiac contractile function. In trained hearts, ND markedly increased heart-to-body weight ratio which was also associated with enhanced baseline cardiac function. ND pretreatment enhanced protective effects of IPC in sedentary group; however, abolished these effects in exercise-trained group. The arrhythmia score was not significantly different between nandrolone-treated groups vs. respective preconditioned groups. Our findings show that ND impairs IPC-induced cardioprotection in exercise-trained rat hearts. Cardiac hypertrophy seems to play a crucial role in this response.

PL - 027 Up-regulation of NRG1 improves cardiac repair in zebra fish and involved in the cardioprotective effects of exercise training in rats of myocardial infarction

Objective Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Exercise training could improve cardiac function following MI. However, the mechanisms are still not well-known. Neuregulin 1 (NRG1)plays an important role in heart development and regeneration.In this study, we investigated the effect of NRG1 on cardiac regeneration in a zebrafish model, detected whether exercise could improve cardiac function through regulating NRG1 expression in infarcted heart and explore the possible role of up-regulation of NRG1 in skeletal muscle play in the cardioprotective effects in rats with MI.&#x0D; Methods Transgenic zebrafish line, cmlc2:CreERandβ-act2:BSNrg1,wereusedto study the effect of NRG1 on heart growth and regeneration after injury. PCNA was detected by immunofluorescence staining andmRNAexpression of gata4, nkx2.5, tbx5, smyd1b, hsp90α and murf were tested by RT-PCR.Sprague-Dawley rats were used to establish MI model and underwent fourweeks of exercise training (ET) or pAAV-{dMCK promoter}rNRG1-eGFP intervention.AG1478 was used asan inhibitor of NRG1/ErbBs signaling pathway. Cardiac function and structure,cardiomyocyte proliferation and NRG1 expression were detected in the heart or skeletal.&#x0D; Results Cardiac-specific overexpression of NRG1 induced cardiac hypertrophy and cardiomyocyte proliferation, regulated the mRNA expression of gata4, nkx2.5, tbx5, smyd1b, hsp90α andmurf in uninjuriedzebrafish, and promote cardiac repair and regeneration after injury in the zebrafish.Exercise activated NRG1/ErbBs signaling pathway, improved cardiac remodeling and heart function, enhanced cardiomyocyte proliferation, reduced cardiomyocyte apoptosis, ROS level and MuRF1 protein expression in rats with MI. BlockingErbB signaling attenuated the ET-induced cardioprotection effects in rat with MI.up-regulation of NRG1 expression in skeletal muscle could increase the protein level of NRG1 in serum and infarcted heart, improve cardiomyocyte proliferation and reduce the level of cardiac fibrosis, finally promote cardiac function.&#x0D; Conclusions Up-regulation of NRG1 expression in the heart or skeletal musclemay be one of the underlying mechanisms of thebeneficial effects of exercise training following MI.

Correlation between the blood level of irisin and the severity of acute myocardial infarction in exercise-trained rats.

Background Acute myocardial infarction is a major cause of death all over the world. Irisin is a novel myokine released after exercise. This work aimed to study the correlation between the serum irisin level and the severity of the acute myocardial infarction in the exercise-trained rats. Methods Forty-eight male rats were classified into four groups (12 for each): group I, control sedentary (C); group II, exercise-trained (EX) (swimming for 8 weeks); group III, isoprenaline-induced infarct (MI); and group IV, exercise-trained infarct (EX-MI) (swimming for 8 weeks followed by isoprenaline-induced infarction). ECG was recorded at start and end of the study, before and after induction of infarction. The serum level of irisin, lipid peroxidation [malondialdehyde (MDA)], total antioxidant status (TAS), creatine phosphokinase-MB (CK-MB), and troponin I was determined. The hearts were excised for histopathology and immunohistochemistry for caspase-3. Results The infarct rats showed significant prolongation in QTc interval and elevation in the ST segment as well as significant elevation of serum CK-MB, troponin I, and MDA, whereas TAS and serum irisin level were significantly decreased. With exercise, we observed a high positive correlation between the serum irisin and QRS duration (+0.643), amplitude (+0.860), and TAS (+0.887). In addition, there was a high negative correlation between the serum irisin and ST elevation (-0.865), QTc (-0.886), CK-MB (-0.891), troponin (-0.882), and MDA (-0.868). This was confirmed by the negative correlation between serum irisin and both collagen deposition and caspase-3 expression (-0.823 and -0.822, respectively). Conclusions We recommend regular exercise or taking recombinant irisin as a supplement to protect at-risk individuals against acute myocardial infarction.

Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue.

The aim of the present work was to study the consequences of chronic exercise training on factors involved in the regulation of mitochondrial remodeling and biogenesis, as well as the ability to produce energy and improve insulin sensitivity and glucose uptake in rat brown adipose tissue (BAT). Male Wistar rats were divided into two groups: (1) control group (C; n = 10) and (2) exercise-trained rats (ET; n = 10) for 8 weeks on a motor treadmill (five times per week for 50 min). Exercise training reduced body weight, plasma insulin, and oxidized LDL concentrations. Protein expression of ATP-independent metalloprotease (OMA1), short optic atrophy 1 (S-OPA1), and dynamin-related protein 1 (DRP1) in BAT increased in trained rats, and long optic atrophy 1 (L-OPA1) and mitofusin 1 (MFN1) expression decreased. BAT expression of nuclear respiratory factor type 1 (NRF1) and mitochondrial transcription factor A (TFAM), the main factors involved in mitochondrial biogenesis, was higher in trained rats compared to controls. Exercise training increased protein expression of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and AMP-activated protein kinase (pAMPK/AMPK ratio) in BAT. In addition, training increased carnitine palmitoyltransferase II (CPT II), mitochondrial F1 ATP synthase α-chain, mitochondrial malate dehydrogenase 2 (mMDH) and uncoupling protein (UCP) 1,2,3 expression in BAT. Moreover, exercise increased insulin receptor (IR) ratio (IRA/IRB ratio), IRA-insulin-like growth factor 1 receptor (IGF-1R) hybrids and p42/44 activation, and decreased IGF-1R expression and IR substrate 1 (p-IRS-1) (S307) indicating higher insulin sensitivity and favoring glucose uptake in BAT in response to chronic exercise training. In summary, the present study indicates that chronic exercise is able to improve the energetic profile of BAT in terms of increased mitochondrial function and insulin sensitivity.

Glucagon-like peptide-1 receptor antagonism impairs basal exercise capacity and vascular adaptation to aerobic exercise training in rats.

Cardiorespiratory fitness (CRF) inversely predicts cardiovascular (CV) mortality and CRF is impaired in people with type 2 diabetes (T2D). Aerobic exercise training (ET) improves CRF and is associated with decreased risk of premature death in healthy and diseased populations. Understanding the mechanisms contributing to ET adaptation may identify targets for reducing CV mortality of relevance to people with T2D. The antihyperglycemic hormone glucagon‐like peptide‐1 (GLP‐1) influences many of the same pathways as exercise and may contribute to CV adaptation to ET. We hypothesized that GLP‐1 is necessary for adaptation to ET. Twelve‐week‐old male Wistar rats were randomized (n = 8–12/group) to receive PBS or GLP‐1 receptor antagonist (exendin 9‐39 (Ex(9‐39)) via osmotic pump for 4 weeks ± ET. CRF was greater with ET (P < 0.01). Ex(9‐39) treatment blunted CRF in both sedentary and ET rats (P < 0.001). Ex(9‐39) attenuated acetylcholine‐mediated vasodilation, while this response was maintained with Ex(9‐39)+ET (P = 0.04). Aortic stiffness was greater with Ex(9‐39) (P = 0.057) and was made worse when Ex(9‐39) was combined with ET (P = 0.004). Ex vivo aortic vasoconstriction with potassium and phenylephrine was lower with Ex(9‐39) (P < 0.0001). Carotid strain improved with PBS + ET but did not change in the Ex(9‐39) rats with ET (P < 0.0001). Left ventricular mitochondrial respiration was elevated with Ex(9‐39) (P < 0.02). GLP‐1 receptor antagonism impairs CRF with and without ET, attenuates the vascular adaptation to ET, and elevates cardiac mitochondrial respiration. These data suggest that GLP‐1 is integral to the adaptive vascular response to ET.

Interleukin-10 and collagen type II immunoexpression are modulated by photobiomodulation associated to aerobic and aquatic exercises in an experimental model of osteoarthritis.

The aim of this study was to compare the effects of photobiomodulation (PBM) associated with an aerobic and an aquatic exercise training on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Fifty male Wistar rats were randomly divided into 5 groups: OA control group (CG), OA plus aerobic training group (AET), OA plus aquatic training group (AQT), OA plus aerobic training associated with PBM group (AETL), OA plus aquatic training associated with PBM group (AQTL). The aerobic training (treadmill; 16m/min; 50min/day) and the aquatic training (water jumping; 50-80% of their body mass) started 4weeks after the surgery and they were performed 3days/week for 8weeks. Moreover, PBM was performed after the physical exercise trainings on the left joint. Morphological characteristics and immunoexpression of IL-10, TGF-β, and collagen type I (Col I) and II (Col II) of the articular cartilage were evaluated. The results showed that all the treated groups (exercise and PBM) presented less intense signs of degradation (measured by histopathological analysis and OARSI grade system). Additionally, aerobic and aquatic exercise training rats (associated or not with PBM) showed increased IL-10 (AET p = 0.0452; AETL p = 0.03; AQTL p = 0.0193) and Col II (AET p = 0.012; AQT p = 0.0437; AETL p = 0.0001; AQTL p = 0.0001) protein expression compared to CG. Furthermore, a statistically higher TGF-β expression was observed in AET (p = 0.0084) and AETL (p = 0.0076) compared to CG. These results suggest that PBM associated with aerobic and aquatic exercise training were effective in mediating chondroprotective effects and maintaining the integrity of the articular tissue in the knees of OA rats.

The Effect of Exercise Training on Sympathetic Vasoconstrictor Responsiveness and Sympatholysis in Female Rats

Our laboratory has previously reported that aerobic exercise training enhances contraction‐mediated inhibition of sympathetic vasoconstriction (sympatholysis) in male rats. Whether aerobic exercise training has a similar effect in female rats has not been established. Therefore, the purpose of the present study was to investigate the hypothesis that aerobic exercise training would blunt sympathetic vasoconstrictor responsiveness and enhance sympatholysis in female rats. Female Sprague‐Dawley rats were randomly assigned to sedentary (n=10) or treadmill exercise training (n=8) groups (15 min at 40 m/min, 5% gradient; 5 d/week) for 10 weeks. Following the completion of the sedentary behavior or exercise training intervention, rats were anaesthetized and instrumented for stimulation of the lumbar sympathetic chain and the measurement of arterial blood pressure and femoral vascular conductance (FVC). The triceps surae muscle group was stimulated to contract rhythmically at 60% of maximal contractile force. The percentage change of FVC (Δ%FVC) in response to sympathetic stimulation delivered at 2 and 5 Hz was determined at rest and during contraction. At rest, sympathetic vasoconstrictor responsiveness (Δ%FVC) was not different (p&gt;0.05) between sedentary and exercise trained rats in response to sympathetic stimulation delivered at 2Hz (Sedentary: −39 ± 12 %; Exercise Trained: −45 ± 9 %) and 5Hz (Sedentary: −57 ± 8 %; Exercise Trained: −61 ± 9 %). Muscle contraction blunted (p&lt;0.05) sympathetic vasoconstrictor responsiveness in both sedentary and exercise trained rats and the magnitude of sympatholysis was not different (p&gt;0.05) between sedentary (2Hz: 24 ± 8 %; 5Hz: 29 ± 10 %) and exercise‐trained (2Hz: 30 ± 10 %; 5Hz: 29 ± 13 %) rats. These data demonstrate that aerobic exercise training does not alter sympathetic vasoconstrictor responsiveness or contraction mediated inhibition of sympathetic vasoconstriction (sympatholysis) in female rats. Further investigation is required to determine why female rats respond differently to exercise training than male rats.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Prostate Cancer Cell Viability and Migration in Serum and Prostate Conditioned Media from Moderate‐Intensity Exercise Trained Rats

Physical activity is associated with diminished risk of several cancers and preclinical studies suggest exercise training may alter tumor cell growth in certain tissues (e.g., adipose). We hypothesized that serum and prostate conditioned media (PCM) from moderate‐intensity exercise trained rats will decrease prostate cancer cell growth, while prostate 5α‐reductase 2 expression will decrease. We evaluated the effects of serum and PCM from moderate‐intensity exercise trained rats on prostate cancer cell viability and migration. In addition, we determined whether moderate‐intensity exercise training would modulate 5α‐reductase 2 protein expression, an essential component of androgen metabolism in prostate cancer. Male Copenhagen rats (~2–3 mo old) were randomly assigned to an exercise‐trained group (n = 10) and a sedentary control group (n = 10). The exercise‐trained rats ran on a motorized treadmill for 5 days/week at 15 m/min, 15° incline for 60 min/day for a 10‐ to 11‐week training period. Serum was collected from both rat groups, and used to supplement media at 5% concentration with and without 5% fetal bovine serum (FBS). Rat prostates were harvested, cut into two approximately equal sections with one section incubated with media for 24 hours to prepare PCM, and immunohistochemistry performed on the other section to quantify 5α‐reductase 2 expression. Dunning R‐3327 AT‐1 prostate cancer cells were grown in PCM, or media supplemented with either 5% serum from the exercise‐trained or sedentary groups with and without 5% FBS for 24–96 hours. Tumor cell viability and migration were determined using MTT and transwell migration assays, respectively. Serum or PCM from exercise‐trained rats did not significantly decrease cell viability compared to serum (e.g. 0.41 ± 0.04 vs. 0.50 ± 0.05 viable cell number, p = 0.14) or PCM (e.g. 0.40 ± 0.07 vs. 0.50 ± 0.08 viable cell number, p = 0.50; all at 48 hour incubation) from sedentary rats, respectively. However, the addition of FBS to serum from exercise‐trained rats significantly decreased cell viability compared to FBS and serum from sedentary rats (e.g. 0.49 ± 0.05 vs. 0.69 ± 0.06 viable cell number, p = 0.02; 48 hour incubation). Serum alone, serum and FBS, or PCM from exercise‐trained rats did not significantly impact cell migration compared to sedentary control (54.7 ± 3.3 vs. 64.2 ± 9.2 cells/field, p = 0.27; 29.3 ± 2.6 vs. 29.3 ± 2.5 cells/field, p &gt; 0.99; 55.9 ± 10.5 vs. 52.8 ± 8.1 cells/field, p = 0.82), respectively. 5α‐reductase 2 in the prostate was not significantly changed with exercise compared to sedentary group (0.87 ± 0.21 vs. 0.78 ± 0.18 positive cells/tissue area (μm2), p = 0.76). In conclusion, prior exercise status did not modify several key characteristics of prostate tumor cell growth and viability from conditioned media from host‐tissue (prostate) or serum in vitro. Whether exercise training alters similar prostate tumor cell growth characteristics in vivo is unknown.Support or Funding InformationAmerican Cancer Society RSG 14‐150‐1‐CCE (BJB)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Effect of Beta‐Adrenergic Receptor Blockade on Sympathetic Vasoconstrictor Responsiveness in Sedentary and Exercise‐Trained Female Rats

Stimulation of the sympathetic nervous system evokes the release of neurotransmitters and produces vasoconstriction that is primarily mediated by the binding of norepinephrine (NE) to alpha‐adrenergic receptors. However, NE may also bind to beta‐ adrenergic receptors and produce vasodilation that opposes vasoconstriction. Therefore, in the present study, we tested the hypothesis that beta‐adrenergic receptor blockade would augment sympathetic vasoconstrictor responsiveness in resting and contracting skeletal muscle of sedentary and exercise trained female rats, demonstrating beta‐adrenergic receptor mediated opposition of vasoconstriction. We also hypothesized that the increase in sympathetic vasoconstrictor responsiveness in the presence of beta‐adrenergic blockade would be larger in exercise‐trained rats, indicating that exercise training augments beta‐adrenergic receptor mediated opposition of vasoconstriction. Female Sprague‐Dawley rats were randomized to Sedentary (n=8, 265 ± 28 g) and Exercise Trained (n=9, 290 ± 27 g) groups. Exercise Trained rats completed a 4‐week treadmill training regimen (5 d/week, 15 min at 40 m/min, 5% gradient). Subsequently, rats were anaesthetized and instrumented for the measurement of femoral vascular conductance (FVC), stimulation of the lumbar sympathetic chain, and contraction of the triceps surae muscle group. The percentage change of femoral vascular conductance (Δ%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction (60% maximal contractile force) before (Control) and after beta‐adrenergic blockade (Propranolol; 0.075 mg/kg body mass, I.V.). Sympathetic vasoconstrictor responsiveness (Δ%FVC) was not different (P &gt; 0.05) between Sedentary and Exercise Trained rats at rest or during contraction. At rest, beta‐adrenergic receptor blockade did not increase (P &gt; 0.05) sympathetic vasoconstrictor responsiveness in Sedentary (Control: 2Hz: −34 ± 9 %, 5Hz: −53 ± 8 %; Propranolol: 2Hz: −31 ± 10 %, 5Hz: −49 ± 8 %) or Exercise Trained (Control: 2Hz: −38 ± 9 %, 5Hz: −57 ± 8 %; Propranolol: 2Hz: −34 ± 7 %, 5Hz: −53 ± 8 %) rats. Similarly, beta‐adrenergic receptor blockade did not increase (P &gt; 0.05) sympathetic vasoconstrictor responsiveness during exercise in Sedentary (Control: 2Hz: −7 ± 4 %, 5Hz: −20 ± 11 %; Propranolol: 2Hz: −6 ± 5 %, 5Hz: −18 ± 10 %) or Exercise Trained (Control: 2Hz: −10 ± 8 %, 5Hz: −28 ± 8 %; Propranolol: 2Hz: −6 ± 5 %, 5Hz: −24 ± 12 %) rats. In conclusion, beta‐adrenergic receptor blockade did not augment sympathetic vasoconstrictor responsiveness in resting or contracting skeletal muscle of sedentary or exercise‐trained female rats, suggesting that beta‐adrenergic receptor mediated vasodilation did not oppose vasoconstriction, regardless of training status.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, and Alberta Advanced Education and Technology.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Moderate exercise training under constant light condition amplifies inflammatory signals through disruption of splenic clock mechanism in osteoarthritic animals

Physical exercise has been recommended for osteoarthritic(OA) patients, the effects of which depends on exercise protocol. Here, we determined whether the benefits of exercise are influenced by lighting condition in the OA rats. Moderate treadmill exercise(Ex) was performed for 4 weeks at ZT14 under 12:12hr light‐dark(L/D) as well as constant light(LL). Intervention was applied for 30 min on 5 days/week. Splenic Cry1 expression was suppressed in the trained rats under constant light condition, leading to upregulation of proinflammatory cytokines mRNA. Moreover, TNFα level in serum was higher in the LL+Ex group than the L/D+Ex group. Constant light combined with exercise exacerbated primary cartilage lesion through an increase of catabolic molecules as well as a transcriptional suppression of anabolic factors. The level of synovial RANKL protein was elevated in the LL+Ex group, leading to loss of tibial trabeculae. And increased joint diameter was not recovered in the exercise‐trained rats under LL condition. Exercise training under constant lighting condition enhanced activation of catabolic machinery in soleus as well as gastrocnemius muscle. Treatment of proinflammatory cytokines disrupted rhythmic expression of catabolic enzymes in C2C12‐derived myotubes. Taken together, lighting condition might be a considerable environmental factor to obtain exercise‐induced benefits.Support or Funding InformationFunding: NRF‐2015R1C1A2A01055691, NRF‐2017R1A2A2A01067169, KGM4611714This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Vasoreactivity of thoracic aorta in Nigella Sativa supplemented and/or exercise trained rats

BackgroundNigella Sativa (NS) induced vasorelaxation of aortic rings upon direct exposure has been documented in literature. This study was conducted to determine whether 8 weeks Nigella Sativa supplementation and/or exercise training may alter vascular sensitivity of rat aorta in normal, healthy rats. MethodsIn this Quasi Experimental Study, forty adult male Wistar albino rats were divided equally into 4 groups. One group served as the control (C), whereas the other three groups were Nigella-treated (N; 800 mg/kg Nigella daily orally via a feeding needle), Exercise-trained (Ex: 18 m/min speed, 2 h duration/day at 32 inclination) and Nigella-treated-exercise-trained (N-Ex: received both Nigella and exercise training). After 8 weeks, rats in all four groups were sacrificed. Their aortic rings were2 mounted in the organ bath. Tension in the aortic rings was measured with an isometric force transducer and recorded with a PowerLab data-acquisition system. Norepinephrine-induced aortic contractions in all four groups were compared by one-way analysis of variance (ANOVA). ResultsThere were statistically insignificant differences in Norepinephrine-induced aortic contractions among all four groups (P value 0.26, 0.18, 0.07, 0.12, 0.58, 0.24, 0.06 with Norepinephrine 0, 10−7, 10−6, 10−5, 10−4, 10−3, 10−2 respectively). Also, no statistical difference was observed in term of body weight, heart weight, left ventricular weight and their indices in all four groups. ConclusionNS supplementation and exercise training alone or in combination; for 8 weeks' duration, may not alter vascular reactivity in normal healthy rats.

Biotin and chromium histidinate improve glucose metabolism and proteins expression levels of IRS-1, PPAR-\u03b3, and NF-\u03baB in exercise-trained rats

BackgroundChromium histidinate (CrHis) and biotin are micronutrients commonly used to improve health by athletes and control glycaemia by patients with diabetes. This study investigates the effects of 8-week regular exercise training in rats together with dietary CrHis and biotin supplementation on glucose, lipids and transaminases levels, as well as protein expression levels of peroxisome proliferator-activated receptor gamma (PPAR-γ), insulin receptor substrate-1 (IRS-1) and nuclear transcription factor kappa B (NF-κB).MethodsA total of 56 male Wistar rats were randomly divided into 8 groups of 7 animals each and treated as follows: Control, CrHis, Biotin, CrHis+Biotin, Exercise, CrHis+Exercise, Biotin+Exercise, and CrHis+Biotin+Exercise. The doses of CrHis and biotin were 400 μg/kg and 6 mg/kg of diet, respectively. The training program consisted of running at 30 m/min for 30 min/day at 0% grade level, 5 days per week, once a day for 6 weeks. Serum glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL), triglycerides (TG), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured with an automatic biochemical analyzer. Muscle and liver PPAR-γ, IRS-1 and NF-κB expressions were detected with real-time polymerase chain reaction.ResultsRegular exercise significantly (p < 0.001) decreased glucose, TC and TG levels, but increased HDL cholesterol. Dietary CrHis and biotin supplementation exhibited a significant (p < 0.001) decrease in glucose (effect size = large; ƞ2 = 0.773) and TG (effect size = large; ƞ2 = 0.802) levels, and increase in HDL cholesterol compared with the exercise group. No significant change in AST and ALT (effect size = none) levels was recorded in all groups (p > 0.05). CrHis/biotin improves the proteins expression levels of IRS-1, PPAR-γ, and NF-κB (effect size: large for all) in the liver and muscle of sedentary and regular exercise-trained rats (p < 0.001).ConclusionsCrHis/biotin supplementation improved serum glucose and lipid levels as well as proteins expression levels of PPAR-γ, IRS-1 and NF-κB in the liver and muscle of exercise-trained rats, with the highest efficiency when administered together. CrHis/biotin may represent an effective nutritional therapy to improve health.