Exercise Model Research Articles

Evaluation of a calculation model to estimate the impact of the COVID-19 pandemic lockdown on visual acuity in neovascular AMD.

PurposeA model was calculated during the first Austrian coronavirus disease-2019 (COVID-19) pandemic lockdown to estimate the effect of a short-term treatment interruption due to healthcare restrictions on visual acuity (VA) in neovascular age-related macular degeneration (nAMD). The model was compared to the real-life outcomes before treatment re-started.MethodsRetrospective data-collection of 142 eyes in 142 patients receiving repeated intravitreal injections with anti-VEGF at a retina unit in Vienna in a personalized pro-re-nata regimen prior to the COVID-19 associated lockdown, when treatment was deferred between March 16 and May 4, 2020. During the lockdown, the preliminary data was integrated into pre-existing formulae based on the natural course of the disease in untreated eyes in the long term. Patients were re-scheduled and treated after gradually opening operating rooms. The calculation model was compared to the effective VA change.ResultsThe model calculated an overall VA loss of 3.5 ± 0.8 letters early treatment diabetes retinopathy study (ETDRS) (p < 0.001 [95% CI:3.3;3.6]) on average compared to 2.5 ± 6 letters ETDRS (p < 0.001 [95% CI:1.5;3.5]) as measured with a mean treatment delay of 61 ± 14 days after previously scheduled appointments. The total difference between the model exercise and the real-life outcomes accounted for 1 ± 5.9 letters ETDRS (p = 0.051 [95% CI: 0.1;1.9]).ConclusionThe herein presented calculation model might not be suitable to estimate the effective VA loss correctly over time, although untreated eyes and eyes under therapy show similarities after short-term treatment interruption. However, this study demonstrated the potentially negative impact of the COVID-19 pandemic lockdown on patients compromised by nAMD.

Modelling of Blood Lactate Time-Courses During Exercise and/or the Subsequent Recovery: Limitations and Few Perspectives.

Because lactate is an important metabolic intermediate and a signalling molecule between/within cells/organs, it appears essential to be able to describe the kinetics of this central molecule, during and/or after physical exercise. The present study aimed to confront three models and their approaches [Freund and co-workers (F&co), Beneke and co-workers (B&co), and Quittmann and co-workers (Q&co)] to investigate the lactate exchange (γ1) and removal (γ2) abilities (min−1) during and/or after exercise. Nine healthy male subjects performed 3- and 6-min easy, moderate, and heavy exercise. Blood lactate concentration (BLC) was measured every 5 s over the entire period of exercise and recovery. Approaches differ depending on the domain in which the model is applied: considering exercise and part of the recovery (B&co and Q&co) or the entire period of recovery (F&co). The different approaches result in differing γ1 and γ2 values. Model fitting is closer to the experimental values following the method (model and approach) of F&co. Complementary analyses show that consideration of (i) exercise drastically impairs the quality of model fitting and therefore the γ1 and γ2 values and (ii) the entire period of recovery considerably improves the quality of fits and therefore of the γ1 and γ2 values. We conclude that (i) it is neither realistic nor reliable to take into account exercise and recovery in the same model and (ii) the longer the period of recovery studied, the better the quality of the γ1 and γ2 values.

Breast cancer chemotherapy vascular toxicity: a review of mediating mechanisms and exercise as a potential therapeutic.

Breast cancer chemotherapy, although very potent against tumour tissue, results in significant cardiovascular toxicity. The focus of research in this area has been predominantly towards cardiotoxicity. There is limited evidence detailing the impact of such treatment on the vasculature despite its central importance within the cardiovascular system and resultant detrimental effects of damage and dysfunction. This review highlights the impact of chemotherapy for breast cancer on the vascular endothelium. We consider the most likely mechanisms of endothelial toxicity to be through direct damage and dysfunction of the endothelium. There are sharp consequences of these detrimental effects as they can lead to cardiovascular disease. However, there is potential for exercise to alleviate some of the vascular toxicity of chemotherapy, and the evidence for this is provided. The potential role of exercise in protecting against vascular toxicity is explained, highlighting the recent in-human and animal model exercise interventions. Lastly, the mediating mechanisms of exercise protection of endothelial health is discussed, focusing on the importance of exercise for endothelial health, function, repair, inflammation and hyperlipidaemia, angiogenesis, and vascular remodelling. These are all important counteracting measures against chemotherapy-induced toxicity and are discussed in detail.

Effect of involuntary chronic physical exercise on beta-amyloid protein in experimental models of Alzheimer's disease: Systematic review and meta-analysis.

The excessive deposition of β-amyloid proteins (Aβ) is directly correlated with the establishment and development of Alzheimer's Disease (AD). Current treatments for AD only reduce symptoms instead of acting on Aβ, the primary etiological agent. Hence, the anti-amyloid effect of regular exercise has been widely investigated as an alternative therapy. This systematic review and meta-analysis examined the anti-amyloid effect of regular physical exercise in animal models of AD. The search was conducted on the electronic databases Pubmed, Embase, Scopus and Web of Science without data limitation and using the following describers: "amyloid beta" (OR senile plaque OR amyloid plaque) and "exercise" (OR physical activity OR training). The risk of bias was evaluated using the SYRCLE's tool. Meta-analyses were conducted using models of random continuous effects. A total of 36 studies were selected and most used: transgenic mice (n=29), treadmill training, duration of 12weeks (interval of 4 to 28weeks), rate of 60min/day (interval of 30min and up until free access) and speed of 12m/min (interval of 3.2 to 32m/min). The hippocampus and cortex were the most frequently investigated regions. Meta-analysis demonstrated a decrease in Aβ with greater effect in unspecified isoforms Meta-analysis demonstrated a decrease in Aβ with greater effect in unspecified isoforms (N=4; SMD=-2.71, IC 95%: -3.59, -1.84, p<0.00001, Q2=3.38, I2=11%) and Aβ1-42 (N=21; SMD=-1.94, IC 95%: -2.37, -1.51, p<0.00001, Q2=33,37, I2=40%). Concerning training, greater effect was found with: 1) swimming (N=4; SMD=-1.98, IC 95%: -3,28 - -0,68, p=0.003, Q2=9.74, I2=69%), 2) moderate intensity (N=4; SMD=-2.03, IC 95%: -3.31 - -0.75, p<0.005, Q2=12.68, I2=76%); 3) duration up to six weeks (N=6; N=6; SMD=-2.35, IC 95%: -3.15 - -1.55, p<0.00001, Q2=8.38, I2=40%); 4) young animals (SMD=-2.00, IC 95%: -2.59 - -1.42, p<0.00001, Q2=24.90, I2=52%); 5) in the amygdala region (N=1; SMD=-8.56, IC 95%: -12.88 - -4.23, p=0.0001) and females (N=4; SMD=-2.14, IC 95%: -3.48 - -0.79, p=0.002, Q2=10.31, I2=71%). However, the reduction of Aβ was associated with decrease of amyloidogenic pathway and increase of non-amyloidogenic. Hence, regular physical exercise demonstrated anti-amyloid effect in experimental models of AD through positive alterations in APP processing through different signaling pathways.

Factors influencing emergency medical competencies of health centers and fire stations in areas that are vulnerable to earthquakes.

ObjectiveThis study aimed to investigate the factors influencing the emergency medical competency (EMC), perceived by the fire station and health center staff, in the areas where of emergency medical vulnerability where earthquakes had occurred.MethodsThis study was conducted between December 2019 and February 2020. A proper questionnaire was created to evaluate EMC in disaster situations and administered to the fire station and the health center groups. Descriptive variables of each group were calculated. The Kendall rank correlation analysis was used to measure the relationships between the demographic variables, disaster-related variables, and EMC. The factors influencing the EMC for both groups were investigated in the linear regression analysis.ResultsFor a total of 200 respondents, the mean scores of EMC were 99.85±21.24 and 95.24±20.05 for the fire station (n=96) and the health center (n=104) groups, respectively (P=0.121). EMC was significantly correlated with age, years of service, job position, natural disaster experience, disaster relief service experience, and joint disaster response exercise (P<0.050). Linear regression analysis revealed that the duration of joint disaster response exercise (β=0.640, t=11.696) in Model 1 (F=136.806, P<0.001), the duration of joint disaster response exercise (β=0.627, P<0.001), and disaster rescue service experience (β=0.124, P<0.001) in Model 2 (F=72.431, P<0.001) were independently associated with EMC improvement.ConclusionOur findings indicate that the disaster preparedness program with a longer duration of joint disaster response exercise and more frequent disaster rescue service experience is necessary for improved and systematic response to a disaster.

Effects of maternal controlled exercise on offspring adiposity and glucose tolerance.

While metabolic disorders such as obesity and diabetes are costly and deadly to the current population, they are also extremely detrimental to the next generation. Much of the current literature focuses on the negative impact of poor maternal choices on offspring disease, while there is little work examining maternal behaviors that may improve offspring health. Research has shown that voluntary maternal exercise in mouse models improves metabolic function in offspring. In this study, we hypothesized that controlled maternal exercise in a mouse model will effect positive change on offspring obesity and glucose homeostasis. Female mice were separated into three groups: home cage, sedentary, and exercise. The sedentary home cage group was not removed from the home cage, while the sedentary wheel group was removed from the cage and placed in an immobile wheel apparatus. The exercise group was removed from the home cage and run on the same wheel apparatus but with the motor activated at 5-10 m/min for 1 h/d prior to and during pregnancy. Offspring were subjected to oral glucose tolerance testing and body composition analysis. There was no significant difference in offspring glucose tolerance or body composition as a consequence of the maternal exercise intervention compared to the sedentary wheel group. There were no marked negative consequences of the maternal controlled exercise intervention. Further research should clarify the potential advantages of the controlled exercise model and improve experimental techniques to facilitate translation of this research to human applications.

GDNF to the rescue: GDNF delivery effects on motor neurons and nerves, and muscle re-innervation after peripheral nerve injuries.

Peripheral nerve injuries commonly occur due to trauma, like a traffic accident. Peripheral nerves get severed, causing motor neuron death and potential muscle atrophy. The current golden standard to treat peripheral nerve lesions, especially lesions with large (≥ 3 cm) nerve gaps, is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur. If not tended early, degeneration of motor neurons and loss of axon regeneration can occur, leading to loss of function. Although surgical procedures exist, patients often do not fully recover, and quality of life deteriorates. Peripheral nerves have limited regeneration, and it is usually mediated by Schwann cells and neurotrophic factors, like glial cell line-derived neurotrophic factor, as seen in Wallerian degeneration. Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth. Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy, sciatic nerve crush, and compression, thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries. Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries. In this review, we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor, the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries, delivery systems, and complementary treatments (electrical muscle stimulation and exercise). Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients’ quality of life.

The effects of aerobic exercise on the intestinal tumors and flora of the ApcMin/+ mouse.

Intestinal tumor is one of the most common tumors that seriously threaten the health of residents all over the world. Studies suggest that the imbalance of intestinal flora is associated with tumorgenesis; meanwhile, long-term regular aerobic exercise can improve the occurrence and development of tumors. However, moderate aerobic exercise affecting the development of intestinal tumors and their related flora has not been explored. Thus, the purpose of our study is to explore the effects of aerobic exercise on intestinal tumor growth and flora changes in ApcMin/+ mice, and try to answer whether there is a correlation between them after exercise intervention. In this study, 18 required ApcMin/+ mice were randomly divided into Model group (n = 6), Exercise group (n = 6), and Aspirin group (positive control, n = 6), while C57BL/6J wild-type mice were used as the blank control group. Each group is given corresponding intervention. Weight monitoring, tumor counts, hematoxylin-eosin staining, TdT-mediated dUTP nick-end labeling (TUNEL) fluorescence assay, immunohistochemistry (IHC), fecal sampling and grouping, and bacterial 16S rDNA gene analysis were completed after 12weeks' intervention for each group of mice. As a result, we were able to show significant improvements in mice' body weight changing rates (Exercise group 8.6% higher than Model control group), tumor numbers (Exercise group 4.33 ± 0.94 vs. Model control group 7.33 ± 2.49, Then put the slides into xylenewith tumor inhibition rate 40.93%), tumor pathological staging (Exercise group mainly low-grade tumorous adenomas vs. Model group mainly high-grade adenomas), and TUNEL staining (Exercise group 8.59% higher positive rate of apoptotic cells in tumors than Model group). The 16s rRNA sequencing analysis results showed that aerobic exercise could regulate the abundance of some genus (16/149, P < 0.01), and the number of intestinal tumors correlates with changes in the abundance of some bacteria in the intestinal flora (positive correlation with probiotics abundance and negative correlation with conditioned pathogens). Changes in flora abundance may be one of the reasons for aerobic exercise to reduce the number of intestinal tumors, probably mediated by cell apoptosis. Future studies should focus on the potential mechanism of aerobic exercise in preventing intestinal tumorgenesis, especially the molecular mechanism through intestinal flora. Aerobic exercise has a preventive effect on intestinal tumors in ApcMin/+ mice, and can regulate the abundance of intestinal flora.

Exercise-induced benefits on glucose handling in a model of diet-induced obesity are reduced by concurrent nicotinamide mononucleotide.

Almost 40% of adults worldwide are classified as overweight or obese. Exercise is a beneficial intervention in obesity, partly due to increases in mitochondrial activity and subsequent increases in nicotinamide adenine dinucleotide (NAD+), an important metabolic cofactor. Recent studies have shown that increasing NAD+ levels through pharmacological supplementation with precursors such as nicotinamide mononucleotide (NMN) improved metabolic health in high-fat-diet (HFD)-fed mice. However, the effects of combined exercise and NMN supplementation are unknown. Thus, here we examined the combined effects of NMN and treadmill exercise in female mice with established obesity after 10 wk of diet. Five-week-old female C57BL/6J mice were exposed to a control diet (n = 16) or HFD. Mice fed a HFD were either untreated (HFD; n = 16), received NMN in drinking water (400 mg/kg; HNMN; n = 16), were exposed to treadmill exercise 6 days/wk (HEx; n = 16), or were exposed to exercise combined with NMN (HNEx; n = 16). Although some metabolic benefits of NMN have been described, at this dose, NMN administration impaired several aspects of exercise-induced benefits in obese mice, including glucose tolerance, glucose-stimulated insulin secretion from islets, and hepatic triglyceride accumulation. HNEx mice also exhibited increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN cotreatment. Our data show that NMN treatment impedes the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.NEW & NOTEWORTHY NMN dampened exercise-induced benefits on glucose handling in diet-induced obesity. NMN administration alongside treadmill exercise enhanced the ratio of antioxidants to prooxidants. We suggest that NMN administration may not be beneficial when NAD+ levels are replete.

Myokine Responses to Exercise in a Rat Model of Low/High Adaptive Potential.

IntroductionAssuming myokines underlie some of the health benefits of exercise, we hypothesised that ‘high responder trainer’ (HRT) rats would exhibit distinct myokine profiles to ‘low responder trainers’ (LRT), reflecting distinct health and adaptive traits.MethodsBlood was collected from LRT and HRT (N=8) rats at baseline (BL), immediately (0h), 1h, and 3h after running; repeated after 3-wks training. Myokines were analysed by ELISA (i.e. BDNF/Fractalkine/SPARC/Irisin/FGF21/Musclin/IL-6).ResultsAt baseline, Musclin (LRT: 84 ± 24 vs HRT: 26 ± 3 pg/ml, P=0.05) and FGF21 (LRT: 133 ± 34 vs HRT: 63.5 ± 13 pg/ml, P=0.08) were higher in LRT than HRT. Training increased Musclin in HRT (26 ± 3 to 54 ± 9 pg/ml, P<0.05) and decreased FGF21 in LRT (133 ± 34 to 60 ± 28 pg/ml, P<0.05). Training increased SPARC (LRT: 0.8 ± 0.1 to 2.1 ± 0.6 ng/ml, P<0.05; HRT: 0.7 ± 0.06 to 1.8 ± 0.3 ng/ml, P=0.06) and Irisin (LRT 0.62 ± 0.1 to 2.6 ± 0.4 ng/ml, P<0.01; HRT 0.53 ± 0.1 to 2.8 ± 0.7 ng/ml, P<0.01) while decreasing BDNF (LRT: 2747 ± 293 to 1081 ± 330 pg/ml, P<0.01; HRT: 1976 ± 328 to 797 ± 160 pg/ml, P<0.05). Acute exercise response of Musclin (AUC) was higher in LRT vs HRT (306 ± 74 vs. 88 ± 12 pg/ml×3h-1, P<0.01) and elevated in HRT after training (221 ± 31 pg/ml×3h-1, P<0.01). Training elevated SPARC (LRT: 2.4 ± 0.1 to 7.7 ± 1.3 ng/ml×3h-1, P<0.05; HRT: 2.5 ± 0.13 to 11.2 ± 2.2 ng/ml×3h-1, P<0.001) and Irisin (LRT: 1.34 ± 0.3 to 9.6 ± 1.7 ng/ml×3h-1, P<0.001; HRT: 1.5 ± 0.5 to 12.1 ± 1.9 ng/ml×3h-1, P<0.0001).ConclusionExercise training alters how myokines are secreted in response to acute exercise. Myokine responses were not robustly linked to adaptive potential in aerobic capacity, making them an unlikely regulator of adaptive traits.

Exploring Exercise-induced BDNF Pathways that affect Tau Dephosphorylation and Episodic Memory in Alzheimer’s Disease: A Systematic Review

Introduction: Research has indicated that exercise improves memory and cognitive function, which can be attributed to an increase in exercise-induced brain-derived neurotrophic factor (BDNF). BDNF has also been suggested to reverse tau aggregation seen in Alzheimer’s disease (AD) via tau dephosphorylation, which can thereby improve memory function. A tyrosine receptor (TrkB) mechanism has been proposed between BDNF and the subsequent tau dephosphorylation. However, the effects of exercise-induced BDNF on tau dephosphorylation and episodic memory remain unclear. Thus, the purpose of the systemic review is to clarify a pathway linking exercise, BDNF, tau dephosphorylation, and episodic memory in AD models. Methods: A comprehensive literature search of peer-reviewed primary and review articles was conducted in the field of neuroscience and memory. Key search terms used in the database were: BDNF, tau, phosphorylation, TrkB, exercise, memory, and Alzheimer’s disease. Results: Evidence suggests that exercise-induced BDNF enhances episodic memory in animal and human studies, and has therapeutic potential for alleviating AD symptoms. Furthermore, bath incubation of BDNF administered to AD-induced human and rodent tissue has demonstrated a rapid tau dephosphorylation effect, specifically through a protein kinase pathway involving PI-3K and AKT, following TrkB binding. Discussion: The memory enhancements demonstrated from increased BDNF production are dependent on exercise. Exercise-induced episodic memory enhancements may be explained by BDNF’s ability to dephosphorylate tau via a TrkB mechanism. Specifically, the PI-3K/AKT pathway is the subsequent downstream signal involved in tau dephosphorylation, since BDNF administration to AD-induced neurons resulted in no dephosphorylation in the presence of a PI-3K inhibitor. Lastly, given BDNF’s ability to dephosphorylate tau in AD models and shift tau accumulation away from the soma, it indicates that exercise may form part of an effective treatment for individuals with AD. Conclusion: Although the research surrounding BDNF and tau dephosphorylation on episodic memory enhancements is extensive, gaps remain about BDNF’s effects in an exercise-induced setting. Further research needs to be conducted to confirm whether exercise-induced BDNF indicates similar effects on episodic memory. This research is also clinically relevant in AD treatment, whereby exercise has the potential to be prescribed concurrently with other therapies.

Regular moderate exercise effects on pro-inflammatory cytokines of diabetic rat’s retina and optic nerve

Objectives: Tissue levels of cytokines represent of inflammation and forewarning of injury. In diabetic patients, these factors increase notably but don’t designate source of them. Retinopathy is one of the complications of diabetes mellitus that probably generates by reason of inflammatory damage in micro vascular or in retinal cells. Exercise decreases blood sugar and diabetic injurious. Investigation of IL-1 and TNF-a in retina in diabetic model rats and exercise effects on them were purposed of this study. Materials and Methods: In this experimental study, 40 adult Wistar male rats (250 ± 50 g) were used. They were randomly divided into four groups (n = 10): (1) Sedentary control (SC) group, (2) sedentary diabetic (SD) group, (3) 8-week healthy exercised (8HE) group and (4) 8-week diabetic exercised (8DE) group. A week after induction of diabetes by injection of streptozotocin, 60 min treadmill exercise and 5 days a week with 22 (m/min) speeds were undertaken. All groups were evaluated in terms of retina and optic nerve tissue levels of TNF-α and IL-1 using ELISA. Results: Based on the results, TNF- α tissue levels were decreased in the 8HE and increased in the 8DE groups compared to control, respectively. Also, no difference was observed in IL-1 tissue levels between exercised and control groups. Conclusion: Long term exercise protocol was useful in healthy rats but don’t decrease of pro-inflammatory retinal complication in diabetes mellitus.

Regular swimming exercise prevented the acute and persistent mechanical muscle hyperalgesia by modulation of macrophages phenotypes and inflammatory cytokines via PPARγ receptors

Physically active individuals are less likely to develop chronic pain, and physical exercise is an established strategy to control inflammatory diseases. Here, we hypothesized that 1) peripheral pro-inflammatory macrophages phenotype contribute to predisposition of the musculoskeletal to chronic pain, and that 2) activation of PPARγ receptors, modulation of macrophage phenotypes and cytokines through physical exercise would prevent persistent muscle pain. We tested these hypotheses using swimming exercise, pharmacological and immunochemical techniques in a rodent model of persistent muscle hyperalgesia. Swimming prevented the persistent mechanical muscle hyperalgesia most likely through activation of PPARγ receptors, as well as activation of PPARγ receptors by 15d-PGJ2 and depletion of muscle macrophages in sedentary animals. Acute and persistent muscle hyperalgesia were characterized by an increase in pro-inflammatory macrophages phenotype, and swimming and the 15d-PGJ2 prevented this increase and increased anti-inflammatory macrophages phenotype. Finally, IL-1β concentration in muscle increased in the acute phase, which was also prevented by PPARγ receptors activation through swimming. Besides, swimming increased muscle concentration of IL-10 in both acute and chronic phases, but only in the persistent phase through PPARγ receptors. Our findings suggest physical exercise activates PPARγ receptors and increases anti-inflammatory responses in the muscle tissue by modulating macrophages phenotypes and cytokines, thereby preventing the establishment of persistent muscle hyperalgesia. These results further highlight the potential of physical exercise to prevent chronic muscle pain.

Analgesic effect of voluntary exercise in a rat model of persistent pain via suppression of microglial activation in the spinal cord.

In this study, we employed a rodent model for persistent allodynia and hyperalgesia to determine whether voluntary exercise could exert analgesic effects on these pain symptoms. Rats were subcutaneously injected with formalin into the plantar surface of the right hind paw to induce mechanical allodynia and hyperalgesia. We assessed the analgesic effects of a voluntary wheel running (VWR) using the von Frey test and investigated microglial proliferation in the dorsal horn of the spinal cord. We also determined the effect of formalin and VWR on the protein expression levels of brain-derived neurotrophic factor (BDNF), its receptor TrkB, and K+-Cl- cotransporter 2 (KCC2), which play a key role in inducing allodynia and hyperalgesia. Rats with access to the running wheels showed beneficial effects on persistent formalin-induced mechanical allodynia and hyperalgesia. The effects of VWR were elicited through the suppression of formalin-induced microglial proliferation, TrkB up-regulation, and KCC2 down-regulation in the spinal cord. BDNF, however, might not contribute to the beneficial effects of VWR. Our results show an analgesic effect of voluntary physical exercise in a rodent model with persistent pain, possibly through the regulation of microglial proliferation and TrkB and KCC2 expression in the spinal cord.

Role of ERβ in adipocyte metabolic response to wheel running following ovariectomy.

Estrogen receptor β (ERb), one of the two major estrogen receptors, acts via genomic and non-genomic signaling pathways to affect many metabolic functions, including mitochondrial biogenesis and respiration. This study assessed the effect of ERb classical genomic activity on adipocyte-specific and -systemic metabolic responses to wheel running exercise in a rodent model of menopause. Female mice lacking the ERb DNA-binding domain (ERbDBDKO, n = 20) and WT (n = 21) littermate controls were fed a high-fat diet (HFD), ovariectomized (OVX), and randomized to control (no running wheel) and exercise (running wheel access) groups and were followed for 8 weeks. Wheel running did not confer protection against metabolic dysfunction associated with HFD+OVX in either ERbDBDKO or WT mice, despite increased energy expenditure. Unexpectedly, in the ERbDBDKO group, wheel running increased fasting insulin and surrogate measures of insulin resistance, and modestly increased adipose tissue inflammatory gene expression (P ≤ 0.05). These changes were not accompanied by significant changes in adipocyte mitochondrial respiration. It was demonstrated for the first time that female WT OVX mice do experience exercise-induced browning of white adipose tissue, indicated by a robust increase in uncoupling protein 1 (UCP1) (P ≤ 0.05). However, KO mice were completely resistant to this effect, indicating that full ERb genomic activity is required for exercise-induced browning. The inability to upregulate UCP1 with exercise following OVX may have resulted in the increased insulin resistance observed in KO mice, a hypothesis requiring further investigation.

Alterations in Serum Myostatin Levels via Swimming Exercise in High Fructose Mediated Metabolic Syndrome Model

Aims: Metabolic syndrome is a table of abdominal diseases characterized by insulin resistance, obesity, dyslipidemia, and hypertension, and it is a serious risk factor for the development of cardiovascular diseases. The purpose of this study was to understand how metabolic syndrome causes a change in myostatin levels, and to understand if swimming exercise have protective and therapeutic effects in fructose mediated metabolic syndrome model by regulating serum myostatin level.&#x0D; Methodology: A total of 21 Sprague Dawley male rats were used in the study. Metabolic syndrome was induced by adding 30% fructose into drinking water for 5 weeks The rats (6-8 weeks old, weighing 200-250 g) were randomly divided into 3 groups as 7 rats in each cage. Swimming exercises were applied three days a week for six weeks. On exercise days, rats were exercised for 20 minutes in a day. Blood was collected from all animals in aprotinin tubes to be used in the necessary analysis with decapitation. Serum samples obtained after centrifugation were kept at -80 ℃ until the assay were performed. In serum samples, myostatin was measured by ELISA method.&#x0D; Results: There was a statistically significant difference resulting from G2, which had the highest value in glucose and triglyceride levels between groups. G2 had the lowest HDL levels. Myostatin levels were significantly higher in G2 compared to other groups.&#x0D; Conclusion: Moderate swimming exercises are protective and therapeutic in preventing chronic diseases such as diabetes, obesity and metabolic syndrome. In line with these results, it can be said that swimming exercise is a therapeutic practice that regulates impaired fasting serum glucose, increased TG levels and decreased HDL levels and downregulates serum myostatin levels.

Muscle Precursor Cells Enhance Functional Muscle Recovery and Show Synergistic Effects With Postinjury Treadmill Exercise in a Muscle Injury Model in Rats

Background: Skeletal muscle injuries represent a major concern in sports medicine. Cell therapy has emerged as a promising therapeutic strategy for muscle injuries, although the preclinical data are still inconclusive and the potential clinical use of cell therapy has not yet been established. Purpose: To evaluate the effects of muscle precursor cells (MPCs) on muscle healing in a small animal model. Study Design: Controlled laboratory study. Methods: A total of 27 rats were used in the study. MPCs were isolated from rat (n = 3) medial gastrocnemius muscles and expanded in primary culture. Skeletal muscle injury was induced in 24 rats, and the animals were assigned to 3 groups. At 36 hours after injury, animals received treatment based on a single ultrasound-guided MPC (105 cells) injection (Cells group) or MPC injection in combination with 2 weeks of daily exercise training (Cells+Exercise group). Animals receiving intramuscular vehicle injection were used as controls (Vehicle group). Muscle force was determined 2 weeks after muscle injury, and muscles were collected for histological and immunofluorescence evaluation. Results: Red fluorescence–labeled MPCs were successfully transplanted in the site of the injury by ultrasound-guided injection and were localized in the injured area after 2 weeks. Transplanted MPCs participated in the formation of regenerating muscle fibers as corroborated by the co-localization of red fluorescence with developmental myosin heavy chain (dMHC)–positive myofibers by immunofluorescence analysis. A strong beneficial effect on muscle force recovery was detected in the Cells and Cells+Exercise groups (102.6% ± 4.0% and 101.5% ± 8.5% of maximum tetanus force of the injured vs healthy contralateral muscle, respectively) compared with the Vehicle group (78.2% ± 5.1%). Both Cells and Cells+Exercise treatments stimulated the growth of newly formed regenerating muscles fibers, as determined by the increase in myofiber cross-sectional area (612.3 ± 21.4 µm2 and 686.0 ± 11.6 µm2, respectively) compared with the Vehicle group (247.5 ± 10.7 µm2), which was accompanied by a significant reduction of intramuscular fibrosis in Cells and Cells+Exercise treated animals (24.2% ± 1.3% and 26.0% ± 1.9% of collagen type I deposition, respectively) with respect to control animals (40.9% ± 4.1% in the Vehicle group). MPC treatment induced a robust acceleration of the muscle healing process as demonstrated by the decreased number of dMHC-positive regenerating myofibers (enhanced replacement of developmental myosin isoform by mature myosin isoforms) (4.3% ± 2.6% and 4.1% ± 1.5% in the Cells and Cells+Exercise groups, respectively) compared with the Vehicle group (14.8% ± 13.9%). Conclusion: Single intramuscular administration of MPCs improved histological outcome and force recovery of the injured skeletal muscle in a rat injury model that imitates sports-related muscle injuries. Cell therapy showed a synergistic effect when combined with an early active rehabilitation protocol in rats, which suggests that a combination of treatments can generate novel therapeutic strategies for the treatment of human skeletal muscle injuries. Clinical Relevance: Our study demonstrates the strong beneficial effect of MPC transplant and the synergistic effect when the cell therapy is combined with an early active rehabilitation protocol for muscle recovery in rats; this finding opens new avenues for the development of effective therapeutic strategies for muscle healing and clinical trials in athletes undergoing MPC transplant and rehabilitation protocols.

Sympathetic neural responses in heart failure during exercise and after exercise training.

The sympathetic nervous system coordinates the cardiovascular response to exercise. This regulation is impaired in both experimental and human heart failure with reduced ejection fraction (HFrEF), resulting in a state of sympathoexcitation which limits exercise capacity and contributes to adverse outcome. Exercise training can moderate sympathetic excess at rest. Recording sympathetic nerve firing during exercise is more challenging. Hence, data acquired during exercise are scant and results vary according to exercise modality. In this review we will: (1) describe sympathetic activity during various exercise modes in both experimental and human HFrEF and consider factors which influence these responses; and (2) summarise the effect of exercise training on sympathetic outflow both at rest and during exercise in both animal models and human HFrEF. We will particularly highlight studies in humans which report direct measurements of efferent sympathetic nerve traffic using intraneural recordings. Future research is required to clarify the neural afferent mechanisms which contribute to efferent sympathetic activation during exercise in HFrEF, how this may be altered by exercise training, and the impact of such attenuation on cardiac and renal function.

A 12-week aerobic exercise intervention results in improved metabolic function and lower adipose tissue and ectopic fat in high-fat diet fed rats.

Investigations of long-term exercise interventions in humans to reverse obesity is expensive and is hampered by poor compliance and confounders. In the present study, we investigated intrahepatic and muscle fat, visceral and subcutaneous fat pads, plasma metabolic profile and skeletal muscle inflammatory markers in response to 12-week aerobic exercise in an obese rodent model. Six-week-old male Wistar rats (n=20) were randomized to chow-fed control (Control, n=5), sedentary high-fat diet (HFD, n=5), chow-fed exercise (Exercise, n=5) and HFD-fed exercise (HFD+Exercise, n=5) groups. The exercise groups were subjected to 12 weeks of motorized treadmill running at a speed of 18 m/min for 30 min/day. Differences in post-intervention measures were assessed by analysis of covariance (ANCOVA), adjusted for baseline bodyweight and pre-intervention measures, where available. Post-hoc analyses were performed with Bonferroni correction. Plasma metabolic profile was worsened and fat pads, ectopic fat in muscle and liver and inflammatory markers in skeletal muscle were elevated in sedentary HFD-fed animals relative to chow-fed controls. HFD+Exercise animals had significantly lower leptin (P=0.0004), triglycerides (P=0.007), homeostatic model assessment of insulin resistance (HOMA-IR; P=0.065), intramyocellular lipids (IMCLs; P=0.003), intrahepatic lipids (IHLs; P<0.0001), body fat% (P=0.001), subcutaneous adipose tissue (SAT; P<0.0001), visceral adipose (P<0.0001) and total fat mass (P<0.0001), relative to sedentary HFD-fed animals, despite only modestly lower bodyweight. Messenger RNA (mRNA) expression of inflammatory markers Interleukin 6 (IL6) and Tumor necrosis factor α (TNFα) were also reduced with aerobic exercise in skeletal muscle. Our results suggest that 12 weeks of aerobic exercise training is effective in improving metabolic health, fat depots, ectopic fat and inflammation even against a high-fat dietary background.

Physical performance level in sarcomeric mitochondria creatine kinase knockout mouse model throughout ageing.

The objective of the present study was to establish the role of sarcomeric mitochondrial creatine kinase (Mt-CK) in muscle energy output during exercise in a murine model of ageing (the Mt-CK knock-out mouse, Mt-CK-/-). Three age groups of Mt-CK-/- mice and control male mice (6, 9, and 18months of age) underwent incremental treadmill running tests. The maximum speed (Vpeak) and maximal oxygen consumption (VO2peak) values were recorded. Urine samples were analyzed using metabolomic techniques. The skeletal muscle (quadriceps) expression of proteins involved in mitochondria biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and dynamin-related GTPase mitofusin 2 (Mnf2) were quantified. The VO2 peak (normalized to heart weight: HW) of 18-month-old (mo) Mt-CK-/- mice was 27% (p<0.001) lower than in 18-mo control mice. The VO2peak/HW ratio was 29% (p<0.001) lower in 18-mo Mt-CK-/- mice than in 6-mo (p<0.001) and 32% (p<0.001) than 9-mo Mt-CK-/- mice. With a 0° slope, Vpeak was 10% (p<0.05) lower in 18-mo Mt-CK-/- mice than in 6-mo Mt-CK-/- mice but did not differ when comparing the 18-mo and 6-mo control groups. The skeletal muscles weight normalized on body weight in 6-mo Mt-CK-/- were 13 to 14% (p<0.001, p<0.05) lower versus the 6-mo control, in addition, the presence of branched-chain amino acids in the urine of 6-mo Mt-CK-/- mice suggests an imbalance in protein turnover (catabolism rather than anabolism) but we did not observe any age-related differences. The expression of PGC-1α and Mnf2 proteins in the quadriceps showed that age-related effects were more prominent than genotype effects. The present study showed ageing is potentialized by Mt-CK deficiency with regard to VO2peak, Vpeak and mitochondrial protein expression. Our results support that Mt-CK-/- mice undergo physiological adaptations, enabling them to survive and to perform as well as wild-type mice. Furthermore, it is possible that these adaptations in Mt-CK-/- mice have a high energy cost and might trigger premature ageing.