Exercise-trained Rats Research Articles

Mitigation of Subsequent Ovariectomy Responses through Prior Exercise Training in Rats.

It is well known that cardiometabolic dysfunction gradually increases after menopause, and the sedentary lifestyle can aggravate this condition. Therefore, we compared the effects of aerobic exercise training during the premenopausal period and after ovariectomy (OVX) on metabolic, hemodynamic, and autonomic parameters in an experimental rat model of menopause. The female rats were divided into four groups: control (C), sedentary OVX (SO), trained OVX (TO), and previously trained OVX (PTO). The PTO group was trained for 4 weeks prior to+8 weeks after OVX, and the TO group trained only after OVX on a motor treadmill. Autonomic modulation was evaluated, white adipose tissue (WAT) was removed and weighed, and lipolysis was assessed. The citrate synthase activity in the soleus muscle was analyzed. The trained groups prevented the impairment of baroreceptor reflex sensitivity in relation to SO; however, only PTO reduced the low-frequency band of the pulse interval compared to SO. PTO reduced the weight of WAT compared to the other groups; lipolysis in PTO was similar to that in C. PTO preserved muscle metabolic injury in all types of fibers analyzed. In conclusion, this study suggests that exercise training should be recommended in a premenopausal model to prevent cardiometabolic and autonomic menopause-induced deleterious effects.

Exercise training-driven exosomal miRNA-323–5p activity suppresses adipogenic conversion of 3T3-L1 cells via the DUSP3/ERK pathway

Adipose-derived stem cell (ASC)-released exosomes (ASCexos) have multiple biological activities. We examined the effect of ASCexos derived from the inguinal adipose tissue of exercise-trained rats (EX-ASCexos) on adipogenic conversion of 3T3-L1 cells and analyzed their microRNA (miRNA) expression profiles. Differentiation of 3T3-L1 cells into adipocytes was performed for 9 d with EX-ASCexos or ASCexos from sedentary control rats (SED-ASCexos), and the expression of proteins and miRNA involved in adipogenic differentiation were determined. EX-ASCexos but not SED-ASCexos attenuated 3T3-L1 adipocyte differentiation with increased phosph-Ser112PPARγ expression, the inactive form of PPARγ. These differentiated adipocytes were also accompanied by increased phosph-Thr202/Tyr204ERK and decreased dual-specificity phosphatase 3 (DUSP3) levels. The exosomal miRNAs miR-323–5p, miR-433–3p, and miR-874–3p were identified specifically in EX-ASCexos. Of these, miR-323–5p mimic replicated the EX-ASCexo-induced suppression of 3T3-L1 adipocyte differentiation and altered adipogenesis-related factor expression. In conclusion, exercise training-driven exosomal miR-323–5p suppressed 3T3-L1 adipogenesis by increasing phosph-Ser112PPARγ expression, while phosph-Thr202/Tyr204ERK accumulation inhibited DUSP3 expression.

Effects of Intravenously Administered Plasma from Exercise-Trained Donors on Microglia and Cytokines in a Transgenic Rat Model of Alzheimer's Disease.

Microglia and inflammation play a significant role in Alzheimer's disease (AD). Physical exercise and peripheral signals can influence microglial activity in the brain. Modulating the inflammatory response in the brain may provide therapeutic approaches for AD. To assess the effects of intravenously administered blood plasma from exercise-trained donor rats on cognitive function, microglia, and cytokine levels in an AD rat model at two different pathological stages; an early pre-plaque stage and a later stage closer to the emergence of extracellular plaques. Male transgenic McGill-R-Thy1-APP rats aged 2 and 5 months received 14 injections over 6 weeks: 1) plasma from exercise-trained rats (ExPlas), 2) plasma from sedentary rats (SedPlas), or 3) saline. Cognitive function was evaluated in a novel object recognition task. Microglia count and morphology were analyzed in cornu ammonis, dentate gyrus, entorhinal cortex, and subiculum. Amyloid plaque number and size were assessed in the rats with the later treatment start. A multiplex assay was used to measure 23 cytokines in cornu ammonis. In rats treated from 2 months of age, ExPlas and SedPlas increased number and length of microglial branches in cornu ammonis and dentate gyrus compared to saline. Only ExPlas-treated rats exhibited similar changes in subiculum, while entorhinal cortex showed no differences across treatments. Microglia count remained unaffected. In rats treated from 5 months of age, there were no significant differences in microglia count or morphology or the number or size of amyloid plaques in any brain region. Compared to both other treatments in early pre-plaque stage rats, SedPlas increased TNF-α levels. ExPlas upregulated GM-CSF, IL-18, and VEGF, while SedPlas increased IL-10 compared to saline. In later-stage rats, ExPlas upregulated IL-17, and SedPlas upregulated TNF-α compared to saline. There were no effects of treatments on recognition memory. Intravenous injections of blood plasma from exercise-trained and sedentary donors differentially modulated microglial morphology and cytokine levels in the AD rat model at an early pre-plaque stage of pathology. Exercised plasma may reduce proinflammatory TNF-α signaling and promote microglial responses to early Aβ accumulation but the lack of treatment effects in the later-stage rats emphasizes the potential importance of treatment timing.

The impact of exercise on gene regulation in association with complex trait genetics.

Endurance exercise training is known to reduce risk for a range of complex diseases. However, the molecular basis of this effect has been challenging to study and largely restricted to analyses of either few or easily biopsied tissues. Extensive transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium has provided a unique opportunity to clarify how exercise can affect tissue-specific gene expression and further suggest how exercise adaptation may impact complex disease-associated genes. To build this map, we integrate this multi-tissue atlas of gene expression changes with gene-disease targets, genetic regulation of expression, and trait relationship data in humans. Consensus from multiple approaches prioritizes specific tissues and genes where endurance exercise impacts disease-relevant gene expression. Specifically, we identify a total of 5523 trait-tissue-gene triplets to serve as a valuable starting point for future investigations [Exercise; Transcription; Human Phenotypic Variation].

Molecular adaptations in response to exercise training are associated with tissue-specific transcriptomic and epigenomic signatures

Regular exercise has many physical and brain health benefits, yet the molecular mechanisms mediating exercise effects across tissues remain poorly understood. Here we analyzed 400 high-quality DNA methylation, ATAC-seq, and RNA-seq datasets from eight tissues from control and endurance exercise-trained (EET) rats. Integration of baseline datasets mapped the gene location dependence of epigenetic control features and identified differing regulatory landscapes in each tissue. The transcriptional responses to 8weeks of EET showed little overlap across tissues and predominantly comprised tissue-type enriched genes. We identified sex differences in the transcriptomic and epigenomic changes induced by EET. However, the sex-biased gene responses were linked to shared signaling pathways. We found that many G protein-coupled receptor-encoding genes are regulated by EET, suggesting a role for these receptors in mediating the molecular adaptations to training across tissues. Our findings provide new insights into the mechanisms underlying EET-induced health benefits across organs.

Cannabinoids improve mitochondrial function in skeletal muscle of exhaustive exercise training rats by inhibiting mitophagy through the PINK1/PARKIN and BNIP3 pathways

Cannabidiol (CBD) is a pure natural phytocannabinoid derived from cannabis that has anti-inflammatory, antiapoptotic and antioxidative stress abilities. In recent years, an increasing number of studies have reported the regulatory effect of CBD on skeletal muscle injury induced by exercise, but its mechanism is still unclear. Mitochondria are the main organelles responsible for the energy supply within eukaryotic cells, and their function has been closely linked to cellular health. Moderate exercise improves mitochondrial function, but the excessive exercise has a negative impact on mitochondria. Therefore, we speculate that CBD may promote exercise induced skeletal muscle cell damage by improving mitochondrial function. In this study, by establishing an animal model of exhaustive exercise training in rats, the protective effect of CBD on skeletal muscle mitochondrial structure and function was elaborated, and the possible molecular mechanism was discussed based on transcriptomics. Our results indicate that skeletal muscle mitochondrial structure and function were improved after CBD intervention. GO and KEGG pathway enrichment analysis showed that exhaustive exercise training induced mitochondrial dysfunction in skeletal muscle is associated with excessive autophagy/mitophagy, the signaling pathways involved in FOXO3 and GABARAPL1 may play important roles. After CBD intervention, the protein expression of PINK1, PARKIN and BNIP3 was down-regulated, indicating that CBD may improve the mitochondrial function by inhibiting mitophagy through the PINK1/PARKIN and BNIP3 pathway.

Exercised blood plasma promotes hippocampal neurogenesis in the Alzheimer's disease rat brain

BackgroundExercise training promotes brain plasticity and is associated with protection against cognitive impairment and Alzheimer's disease (AD). These beneficial effects may be partly mediated by blood-borne factors. Here we used an in vitro model of AD to investigate effects of blood plasma from exercise-trained donors on neuronal viability, and an in vivo rat model of AD to test whether such plasma impacts cognitive function, amyloid pathology, and neurogenesis. MethodsMouse hippocampal neuronal cells were exposed to AD-like stress using amyloid-β and treated with plasma collected from human male donors 3 h after a single bout of high-intensity exercise. For in vivo studies, blood was collected from exercise-trained young male Wistar rats (high-intensity intervals 5 days/week for 6 weeks). Transgenic AD rats (McGill-R-Thy1-APP) were injected 5 times/fortnight for 6 weeks at 2 months or 5 months of age with either (a) plasma from the exercise-trained rats, (b) plasma from sedentary rats, or (c) saline. Cognitive function, amyloid plaque pathology, and neurogenesis were assessed. The plasma used for the treatment was analyzed for 23 cytokines. ResultsPlasma from exercised donors enhanced cell viability by 44.1% (p = 0.032) and reduced atrophy by 50.0% (p < 0.001) in amyloid-β-treated cells. In vivo exercised plasma treatment did not alter cognitive function or amyloid plaque pathology but did increase hippocampal neurogenesis by ∼3 fold, regardless of pathological stage, when compared to saline-treated rats. Concentrations of 7 cytokines were significantly reduced in exercised plasma compared to sedentary plasma. ConclusionOur proof-of-concept study demonstrates that plasma from exercise-trained donors can protect neuronal cells in culture and promote adult hippocampal neurogenesis in the AD rat brain. This effect may be partly due to reduced pro-inflammatory signaling molecules in exercised plasma.

Comparison of interleukin-6, oxidant and antioxidant levels in the kidneys of the trained and untrained rats following exhaustive exercise

In this study, the cytokine response (interleukin-6; IL-6), free oxygen radicals which are claimed to be responsible for the damage in the kidney tissue of exercise-trained rats and untrained-rats, and antioxidant levels were investigated after being forced to an exhausting run. Forty male Wistar albino rats were assigned to the following groups: sedentary controls (C); untrained animals that acutely completed the exhaustive exercise and were sacrificed immediately after exhaustion (UT-i) or 1 day after exhaustion (UT-1); and long-term trained animals that completed the exhaustive exercise and were sacrificed immediately after exhaustion (T-i) or 1 day after exhaustion (T-1). In UT-i and 1 day after exhaustion (T-1) groups, total oxidant status levels were increased compared to controls (P&lt;0.05). IL-6, which is reported to have an anti-inflammatory effect in exercise, did not increase in untrained group immediately, but started to increase 1 day after exhaustion compared to controls. IL-6 levels were significantly increased in the T-i and T-1 groups compared to the control and UT-i groups (P&lt;0.05). The level of total antioxidant status did not show a significant increase in the UT-i group but started to rise after exhaustion the T-1 group. IL-6 levels were significantly increased in the T-i and T-1 groups compared to the control, UT-i, and UT-1 groups (P&lt;0.05). As a result, while oxidant stress and antioxidant mechanism increased immediately in the trained group, IL-6 increased significantly immediately and 1 day later. In the untrained group, however, an increase was observed in oxidant stress, antioxidant mechanism, and IL-6 levels after 1 day.

M6A methyltransferase WTAP regulates myocardial ischemia reperfusion injury through YTHDF1/FOXO3a signaling.

N6-methyladenosine (m6A) is emerging as an essential regulator in the progression of myocardial ischemia reperfusion (I/R) injury. However, the in-depth functions and mechanisms for m6A are still unclear. This work aimed to explore the potential functions and mechanisms for myocardial I/R injury. In this study, m6A methyltransferase WTAP and m6A modification level elevated in the hypoxia/reoxygenation (H/R) induced rat cardiomyocytes (H9C2) and I/R injury rat model. Bio-functional cellular experiments demonstrated that knockdown of WTAP remarkably released the proliferation and reduced the apoptosis and inflammatory cytokines induced by H/R. Moreover, exercise training alleviated WTAP level in exercise-trained rats. Mechanistically, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) revealed that a remarkable m6A modification site was found in the 3'-UTR of FOXO3a mRNA. Moreover, WTAP triggered the installation of m6A modification on FOXO3a mRNA through m6A reader YTHDF1, thereby enhancing the stability of FOXO3a mRNA. Collectively, WTAP/YTHDF1/m6A/FOXO3a axis regulates the myocardial I/R injury progression, which provides new insights for the treatment of myocardial injury.

Voluntary wheel exercise training affects locomotor muscle, but not the diaphragm in the rat.

Introduction: Functional tests and training regimens intensity-controlled by an individual are used in sport practice, clinical rehabilitation, and space medicine. The model of voluntary wheel running in rats can be used to explore molecular mechanisms of such training regimens in humans. Respiratory and locomotor muscles demonstrate diverse adaptations to treadmill exercise, but the effects of voluntary exercise training on these muscle types have not been compared yet. Therefore, this work aimed at the effects of voluntary ET on rat triceps brachii and diaphragm muscles with special attention to reactive oxygen species, which regulate muscle plasticity during exercise. Methods: Male Wistar rats were distributed into exercise trained (ET) and sedentary (Sed) groups. ET group had free access to running wheels, running activity was continuously recorded and analyzed using the original hardware/software complex. After 8weeks, muscle protein contents were studied using Western blotting. Results: ET rats had increased heart ventricular weights but decreased visceral/epididymal fat weights and blood triglyceride level compared to Sed. The training did not change corticosterone, testosterone, and thyroid hormone levels, but decreased TBARS content in the blood. ET rats demonstrated higher contents of OXPHOS complexes in the triceps brachii muscle, but not in the diaphragm. The content of SOD2 increased, and the contents of NOX2 and SOD3 decreased in the triceps brachii muscle of ET rats, while there were no such changes in the diaphragm. Conclusion: Voluntary wheel running in rats is intensive enough to govern specific adaptations of muscle fibers in locomotor, but not respiratory muscle.

Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

Regular physical exercise has been investigated as a primary preventive measure of several chronic diseases and premature death. Moreover, it has been shown to synchronize responses across multiple organs. In particular, hepatic tissue has proven to be a descriptive matrix to monitor the effect of physical activity. In this study, we performed an untargeted metabolomics-based analysis of hepatic tissue extracts from rats that have undergone either lifelong or chronic exercise training. For this purpose, 56 hepatic samples were collected and were analyzed by UHPLC-TOF-MS in negative ionization mode. This approach involved untargeted metabolite detection on hepatic tissue extracts accompanied by an in-house retention time/accurate mass library enabling confident metabolite identification. Unsupervised (PCA) and supervised (OPLS-DA) multivariate analysis showed significant metabolic perturbation on a panel of 28 metabolites, including amino acids, vitamins, nucleotides, and sugars. The training regime employed in this study resulted in a probable acceleration of the bioenergetic processes (glycolysis, glycogen metabolism), promoted catabolism of purines, and supplied biosynthetic precursors via the pentose phosphate pathway and pentose and glucuronate interconversions. Overall, the applied methodology was able to discriminate the different training schedules based on the rat liver metabolome.

The Effect of Voluntary Physical Activity in an Enriched Environment and Combined Exercise Training on the Satellite Cell Pool in Developing Rats.

Aim: Postnatal skeletal muscle growth is strongly associated with a satellite cell pool. Early adolescence might be a crucial period when different exercise training interventions have specific consequence on satellite cells. Pax7 and MyoD have been suggested as the leading indicators of satellite cell activation. Methods: In this study, pre-adolescent male rats (n = 18) were either subjected to an enriched environment that facilitated physical activities or combined training or control for three weeks. The flexor hallucis longus muscle was removed for biochemical and histochemical analysis. Results: Findings demonstrated that exercise trained rats displayed high levels of serum IGF-1 (p <0.05). There was an increase in Pax7 (p <0.05) and MyoD (p <0.001) mRNA expression. A significant increase in the mean fiber area (p <0.01), satellite cell (p <0.001), and myonuclear numbers (p <0.01) were also observed in both intervention groups. Importantly, enriched rats showed lower corticosterone levels (p <0.05) compared to training ones. Regarding performance, trained and enriched rats had significant improvement in forelimb grip strength (p <0.01) and load-carrying capacity (p <0.05). Conclusion: Type of physical exercise is an essential part in changing satellite cells pool. Different and frequent physical activities in an enriched environment can be effective for muscle development.

Promotion of aging heart function and its redox balance following hind-limb blood flow restriction plus endurance exercise training in rats: klotho and PGC1-α as involving candidate molecules.

Mild to moderate-intensity endurance exercise training combined with hind-limb blood flow restriction (BFR) induces elderly heart rejuvenation and improves cardiac inotropy and resistance to ischemia. However, the mediators of these beneficial effects are still not well known. The present study investigated the possible role of some important molecules in the mediatory of this model of exercise training in the promotion of heart health in aged rats. Male old Wistar rats randomly were divided into control-sham (CTL), hind limbs blood flow restriction (BFR), sham-operated plus 10weeks' treadmill exercise training (Ex), and BFR plus exercise (BFR + Ex) groups. Left ventricular end-diastolic pressure (LVEDP), contractility, and Tau indices were measured. ELISA and western blot tests were used for measuring determined cardiac biochemical factors. BFR + Ex displayed significantly lower LVEDP (P < 0.05 and P < 0.01 vs. Ex, and other groups, respectively), improved heart cardiac contractility (P < 0.01), and significantly reduced Tau index in comparison with other groups. BFR + Ex significantly reduced both BAX and BAX to BCL2 ratio (P < 0.05) and as well MDA to TAC ratio (P < 0.05, compared to the CTL group). Also, BFR + Ex significantly increased the level of klotho (P < 0.05) and PGC1-α (P < 0.001) proteins compared to the CTL group but had no significant effect on P-STAT3 expression. Exercise training alone increased Apelin protein (P < 0.05). Our findings suggest that mild to moderate BFR endurance training improves heart performance in the aging rat partly through ameliorating apoptosis, recovering redox balance, improving the longevity factor klotho, and increasing the key energy metabolism regulator PGC1-α.

The mitochondrial signaling peptide MOTS-c improves myocardial performance during exercise training in rats

Cardiac remodeling is a physiological adaptation to aerobic exercise and which is characterized by increases in ventricular volume and the number of cardiomyocytes. The mitochondrial derived peptide MOTS-c functions as an important regulator in physical capacity and performance. Exercise elevates levels of endogenous MOTS-c in circulation and in myocardium, while MOTS-c can significantly enhance exercise capacity. However, the effects of aerobic exercise combined with MOTS-c on cardiac structure and function are unclear. We used pressure–volume conductance catheter technique to examine cardiac function in exercised rats with and without treatment with MOTS-c. Surprisingly, MOTS-c improved myocardial mechanical efficiency, enhanced cardiac systolic function, and had a tendency to improve the diastolic function. The findings suggest that using exercise supplements could be used to modulate the cardiovascular benefits of athletic training.

Alterations in renin-angiotensin receptors are not responsible for exercise preconditioning of skeletal muscle fibers

Endurance exercise training promotes a protective phenotype in skeletal muscle known as exercise preconditioning. Exercise preconditioning protects muscle fibers against a variety of threats including inactivity-induced muscle atrophy. The mechanism(s) responsible for exercise preconditioning remain unknown and are explored in these experiments. Specifically, we investigated the impact of endurance exercise training on key components of the renin-angiotensin system (RAS). The RAS was targeted because activation of the classical axis of the RAS pathway via angiotensin II type I receptors (AT1Rs) promotes muscle atrophy whereas activation of the non-classical RAS axis via Mas receptors (MasRs) inhibits the atrophic signaling of the classical RAS pathway. Guided by prior studies, we hypothesized that an exercise-induced decrease in AT1Rs and/or increases in MasRs in skeletal muscle fibers is a potential mechanism responsible for exercise preconditioning. Following endurance exercise training in rats, we examined the abundance of AT1Rs and MasRs in both locomotor and respiratory muscles. Our results indicate that endurance exercise training does not alter the protein abundance of AT1Rs or MasRs in muscle fibers from the diaphragm, plantaris, and soleus muscles compared to sedentary controls (p ​> ​0.05). Furthermore, fluorescent angiotensin II (AngII) binding analyses confirm our results that exercise preconditioning does not alter the protein abundance of AT1Rs in the diaphragm, plantaris, and soleus (p ​> ​0.05). This study confirms that exercise-induced changes in RAS receptors are not a key mechanism that contributes to the beneficial effects of exercise preconditioning in skeletal muscle fibers.

Effect of exercise training in rats exposed to chronic hypoxia: Application for Monge's disease.

Physical exercise may improve hematological conditions in high altitude dwellers suffering from Chronic Mountain Sickness (CMS), in reducing hemoglobin concentration. Therefore, the present study aimed to characterize the effects of 1‐month exercise training session in a model of rats exposed to chronic hypoxia. Four groups of male rats were studied: normoxic sedentary (NS, n = 8), normoxic training (NT, n = 8), hypoxic sedentary (HS, n = 8), and hypoxic training group (HT, n = 8). Hypoxic groups were exposed to hypobaric hypoxia for one month (PB =433 Torr). Training intensity was progressively increased from a running speed of 10.4 to 17.8 m/min. Chronic hypoxia led to an increase in hematocrit (HCT) associated with a decrease in plasma volume despite an increase in water intake. Training led to a reduction in HCT (p < 0.01), with a non‐significant increase in plasma volume and weight gain. Hypoxia and training had inhibitory effects on haptoglobin (NS group: 379 ± 92; HT: 239 ± 34 µg/ml, p < 0.01). Chronic hypoxia and exercise training increased SpO2 measured after acute hypoxic exposure. Training blunted the decrease in V˙ O2 peak, time of exhaustion, and maximum speed associated with chronic exposure to hypoxia. Chronic hypoxia led to a right ventricular hypertrophy, which was not corrected by 1‐month exercise training. Altogether, by decreasing hematocrit, reducing body weight, and limiting performance decrease, training in hypoxia may have a beneficial effect on excessive erythropoiesis in chronic hypoxia. Therefore, regular exercise training might be beneficial to avoid worsening of CMS symptoms in high altitude dwellers and to improve their quality of life.

Mechanical and Structural Remodeling of Cardiac Muscle after Aerobic and Resistance Exercise Training in Rats.

Aerobic and resistance exercise training results in distinct structural changes of the heart. The mechanics of how cardiac cells adapt to resistance training and the benefits to cells when combining aerobic and resistance exercise remains largely unknown. The purpose of this study was to compare mechanical adaptations of skinned cardiac fiber bundles after chronic resistance, aerobic and combined exercise training in rats. We hypothesized that differences in mechanical function on the fiber bundle level coincide with differences previously reported in the structure of the heart. Twelve-week-old rats were assigned to (i) an aerobic running group (n = 6), (ii) a ladder climbing resistance group (n = 6), (iii) a combination group subjected to aerobic and resistance training (n = 6), or (iv) a sedentary (control) group (n = 5). Echocardiography was used to measure cardiac structural remodeling. Skinned cardiac fiber bundles were used to determine active and passive force properties, maximal shortening velocity, and calcium sensitivity. Aerobically trained animals had 43%-49% greater ventricular volume and myocardial thickness, and a 4%-17% greater shortening velocity and calcium sensitivity compared with control group rats. Resistance-trained rats had 37%-71% thicker ventricular walls, a 56% greater isometric force production, a 9% greater shortening velocity, and a 4% greater calcium sensitivity compared with control group rats. The combination exercise-trained rats had 25%-43% greater ventricular volume and myocardial wall thickness, a 55% greater active force production, a 7% greater shortening velocity, and a 60% greater cross-bridge cooperativity compared with control group rats. The heart adapts differently to each exercise modality, and a combination of aerobic and resistance training may have the greatest benefit for cardiac health and performance.

Intermittent Hypoxia Exposure Can Prevent Reductions in Hemoglobin Concentration After Intense Exercise Training in Rats.

Intense exercise training can induce low concentrations of hemoglobin, which may be followed by maladaptation. Therefore, it is important for athletes to prevent low concentrations of hemoglobin during intense exercise training. In this study, we explored whether different protocols of intermittent hypoxic exposure (IHE, normobaric hypoxia, 14.5% O2) could prevent the exercise training-induced reduction in hemoglobin concentration in rats. Six-week-old male Sprague-Dawley rats were subjected to progressive intense treadmill exercise training over three weeks followed by three weeks of training with IHE after exercise. IHE lasted either 1 h, 2 h, or 1 h + 1 h (separated by a 3-h interval) after the exercise sessions. Hematological parameters, including hemoglobin concentration [(Hb)], red blood cells (RBCs), and hematocrit (Hct), and both renal and serum erythropoietin (EPO) were examined. We found that intense exercise training significantly reduced [Hb], RBCs, Hct, food intake and body weight (P < 0.01). Analysis of reticulocyte hemoglobin content (CHr) and reticulocyte counts in the serum of the rats suggested that this reduction was not due to iron deficiency or other cofounding factors. The addition of IHE after the intense exercise training sessions significantly alleviated the reduction in [Hb], RBCs, and Hct (P < 0.05) without an obvious impact on either food intake or body weight (P > 0.05). Increase in reticulocyte count in the rats from the IHE groups (P < 0.05 or P < 0.01) suggests that IHE promotes erythropoiesis to increase the hemoglobin concentration. Furthermore, the addition of IHE after the intense exercise training sessions also significantly increased the concentration of renal EPO (P < 0.05), although the increase of the serum EPO level was statistically insignificant (P > 0.05). The different IHE protocols were similarly effective at increasing renal EPO and preventing the training-induced decreases in [Hb], RBCs, and Hct. Collectively, this study suggests that IHE may be used as a new strategy to prevent intense exercise training-induced reductions in [Hb], and deserves future exploration in athletes.

Homeobox A5 and C10 genes modulate adaptation of brown adipose tissue during exercise training in juvenile rats.

What is the central question of this study? Exercise can stimulate brown adipose tissue (BAT) with subsequent increase in uncoupling protein 1 expression and mitochondrial biogenesis. In that case, do BAT-specific Hox genes modify BAT functioning and cause uncoupling protein expression changes due to exercise? What is the main finding and its importance? Exercise enhanced brown adipocyte markers, with significant upregulation of HoxA5 and downregulation of HoxC10 mRNA expression in rat BAT. HoxA5 and HoxC10 are thus likely to play distinct roles in exercise-induced changes in BAT markers during the early postnatal period. These findings provide new insight into the mechanisms underlying exercise-induced changes in BAT function. Brown adipose tissue (BAT) recruitment is involved in increased energy expenditure associated with cold exposure and exercise training. We explored whether exercise training induced changes in expression levels of brown adipocyte-selective factors and Homeobox (Hox) genes during the post-weaning growth period of male Wistar rats. Relative to total body weight, BAT weights alone were lower in exercise-trained (EX) rats compared to sedentary control (SED) rats. mRNA expression of HoxA5 was higher and that of HoxC10 was lower in EX rats than in SED rats, accompanied by both higher citrate synthase activity and protein expression levels for uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor (PPAR) α, and PPARγ-coactivator (PGC)-1α. HoxA5 knockdown with siRNA reduced the expression of PR-domain containing 16 (Prdm16), cell death-inducing DNA fragmentation factor-α-like effector A (Cidea) gene, type 2 deiodinase mRNA, and PRDM16 protein. Comparatively, HoxC10 knockdown with siRNA enhanced mRNA expression of Prdm16, Pparα and Pgc1α and protein expression of UCP1, PPARα and PGC1α in brown adipocytes. The stimulation of brown adipocytes with isoproterenol, a β-adrenoceptor agonist, caused a phenomenon similar to the effect of exercise training on the genes tested: upregulation of HoxA5 mRNA, downregulation of HoxC10 mRNA, and increased protein expression for UCP1 and PGC1α. Collectively, HoxA5 and HoxC10 may have unique functions that contribute to modulating the expression of BAT-selective markers in BAT of juvenile rats during exercise training. The study findings regarding activation and recruitment of BAT during exercise training have implications for anti-obesity management.

HHOM-051608 A Whey Protein Formulation Fortified with Herbal Actives Improves Exercise Performance and Muscle Strength: A Preclinical Study

Context: The lifestyle of individuals is changing rapidly in today’s world and physical fitness is an essential requirement to keep oneself fit and healthy. Nutritional supplements could improve physical fitness by modulating energy metabolism, oxidative processes, and perceived fatigue. Aim: This study aimed to evaluate the effects of HHOM-051608, which is a first-of-its-kind whey protein supplement, packed with naturally rich essential amino acids and herbal ingredients to improve the exercise performance, energy metabolism, and physical endurance. Setting and study design: Thirty-two male Wistar rats were divided into four groups of eight each. Group 1 served as sedentary control; group 2 was sedentary rats treated with HHOM-051608 (2 g/kg b.w.); group 3 was exercise training control, and group 4 was exercise training rat treated with HHOM-051608 (2g/kg b.w.). Methods: The exercise training rats were trained on a motorized rat treadmill at a constant speed for 8 weeks. After 8 weeks, all animals were subjected to a grip strength test followed by a treadmill endurance test. Statistical analysis: The results were statistically analyzed by one-way analysis of variance followed by Tukey comparison test, using Prism GraphPad 6.07 (GraphPad Software Inc, San Diego, CA, USA). A P value < 0.05 was considered statistically significant. Results: HHOM-051608 supplemented animals showed a significant increase in grip strength and run time on the treadmill. Conclusion: HHOM-051608 has improved the exercise performance, muscle strength, and muscle glycogen. Thus can be recommended to enhance exercise performance, build muscle mass and decrease muscle soreness.