Impact of High-Fat Diet and Exercise on Bone and Bile Acid Metabolism in Rats.

Bile acids help facilitate intestinal lipid absorption and have endocrine activity in glucose, lipid and bone metabolism. Obesity and exercise influence bile acid metabolism and have opposite effects in bone. This study investigates if regular exercise helps mitigate the adverse effects of obesity on bone, potentially by reversing alterations in bile acid metabolism. Four-month-old female Sprague Dawley rats either received a high-fat diet (HFD) or a chow-based standard diet (lean controls). During the 10-month study period, half of the animals performed 30 min of running at moderate speed on five consecutive days followed by two days of rest. The other half was kept inactive (inactive controls). At the study's end, bone quality was assessed by microcomputed tomography and biomechanical testing. Bile acids were measured in serum and stool. HFD feeding was related to reduced trabecular (-33%, p = 1.14 × 10-7) and cortical (-21%, p = 2.9 × 10-8) bone mass and lowered femoral stiffness (12-41%, p = 0.005). Furthermore, the HFD decreased total bile acids in serum (-37%, p = 1.0 × 10-6) but increased bile acids in stool (+2-fold, p = 7.3 × 10-9). These quantitative effects were accompanied by changes in the relative abundance of individual bile acids. The concentration of serum bile acids correlated positively with all cortical bone parameters (r = 0.593-0.708), whilst stool levels showed inverse correlations at the cortical (r = -0.651--0.805) and trabecular level (r = -0.656--0.750). Exercise improved some trabecular and cortical bone quality parameters (+11-31%, p = 0.043 to 0.001) in lean controls but failed to revert the bone loss related to the HFD. Similarly, changes in bile acid metabolism were not mitigated by exercise. Prolonged HFD consumption induced quantitative and qualitative alterations in bile acid metabolism, accompanied by bone loss. Tight correlations between bile acids and structural indices of bone quality support further functional analyses on the potential role of bile acids in bone metabolism. Regular moderate exercise improved trabecular and cortical bone quality in lean controls but failed in mitigating the effects related to the HFD in bone and bile acid metabolism.

Aerobic exercise-induced HIF-1α upregulation in heart failure: exploring potential impacts on MCT1 and MPC1 regulation.

BACKGROUND: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. METHODS: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. RESULTS: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. CONCLUSION: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1.

Targeted expression of heme oxygenase-1 in satellite cells improves skeletal muscle pathology in dystrophic mice.

BACKGROUND: Adult muscle-resident myogenic stem cells, satellite cells (SCs), that play non-redundant role in muscle regeneration, are intrinsically impaired in Duchenne muscular dystrophy (DMD). Previously we revealed that dystrophic SCs express low level of anti-inflammatory and anti-oxidative heme oxygenase-1 (HO-1, HMOX1). Here we assess whether targeted induction of HMOX1 affect SC function and alleviates hallmark symptoms of DMD. METHODS: We generated double-transgenic mouse model (mdx;HMOX1Pax7Ind) that allows tamoxifen (TX)-inducible HMOX1 expression in Pax7 positive cells of dystrophic muscles. Mdx;HMOX1Pax7Ind and control mdx mice were subjected to 5-day TX injections (75 mg/kg b.w.) followed by acute exercise protocol with high-speed treadmill (12 m/min, 45 min) and downhill running to worsen skeletal muscle phenotype and reveal immediate effects of HO-1 on muscle pathology and SC function. RESULTS: HMOX1 induction caused a drop in SC pool in mdx;HMOX1Pax7Ind mice (vs. mdx counterparts), while not exaggerating the effect of physical exercise. Upon physical exercise, the proliferation of SCs and activated CD34- SC subpopulation, was impaired in mdx mice, an effect that was reversed in mdx;HMOX1Pax7Ind mice, however, both in vehicle- and TX-treated animals. This corresponded to the pattern of HO-1 expression in skeletal muscles. At the tissue level, necrotic events of selective skeletal muscles of mdx mice and associated increase in circulating levels of muscle damage markers were blunted in HO-1 transgenic animals which showed also anti-inflammatory cytokine profile (vs. mdx). CONCLUSIONS: Targeted expression of HMOX1 plays protective role in DMD and alleviates dystrophic muscle pathology.

Effects of conditioning on the left ventricular function of young purebred Arabian horses.

The effects of conditioning on cardiac function in young horses is still unknown. For this reason, this study evaluated the left ventricular (LV) function of young horses by echocardiography after six weeks of conditioning. Fourteen untrained young purebred Arabian horses were evaluated at rest and after a stress test (ST) before and after a six-week conditioning program. There was an increase in V4 (p < 0.001) after conditioning, as well as a reduction in both heart rate (HR) at rest and peak HR during the ST (p < 0.001). There was also a reduction in internal diameter, along with an increase in interventricular septal, free wall and mean thicknesses and LV mass (p < 0.05). After the ST, the conditioned animals showed higher values of velocity time integral, stroke volume, systolic and cardiac indices, ejection (ET) and deceleration times (DT), end-diastolic volume, time to onset of radial myocardial velocity during early diastole and time to peak of transmitral flow velocity, in addition to reduced pre-ejection period (PEP), PEP/ET ratio and mean velocity of circumferential fiber shortening (p < 0.05). The conditioning protocol promoted physiological adaptations that indicate an improvement in the animals' aerobic capacity associated with an enhanced left ventricular function.

Effects of endurance training under calorie restriction on energy substrate metabolism in mouse skeletal muscle and liver.

We investigated whether calorie restriction (CR) enhances metabolic adaptations to endurance training (ET). Ten-week-old male Institute of Cancer Research (ICR) mice were fed ad libitum or subjected to 30% CR. The mice were subdivided into sedentary and ET groups. The ET group performed treadmill running (20-25 m/min, 30 min, 5 days/week) for 5 weeks. We found that CR decreased glycolytic enzyme activity and monocarboxylate transporter (MCT) 4 protein content, while enhancing glucose transporter 4 protein content in the plantaris and soleus muscles. Although ET and CR individually increased citrate synthase activity in the plantaris muscle, the ET-induced increase in respiratory chain complex I protein content was counteracted by CR. In the soleus muscle, mitochondrial enzyme activity and protein levels were increased by ET, but decreased by CR. It has been suggested that CR partially interferes with skeletal muscle adaptation to ET.

The influence of endurance exercise training on myocardial fibrosis and arrhythmogenesis in a coxsackievirus B3 myocarditis mouse model.

Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.

Long-Term High-Fat Diet Limits the Protective Effect of Spontaneous Physical Activity on Mammary Carcinogenesis.

Breast cancer is influenced by factors such as diet, a sedentary lifestyle, obesity, and postmenopausal status, which are all linked to prolonged hormonal and inflammatory exposure. Physical activity offers protection against breast cancer by modulating hormones, immune responses, and oxidative defenses. This study aimed to assess how a prolonged high-fat diet (HFD) affects the effectiveness of physical activity in preventing and managing mammary tumorigenesis. Ovariectomised C57BL/6 mice were provided with an enriched environment to induce spontaneous physical activity while being fed HFD. After 44 days (short-term, ST HFD) or 88 days (long-term, LT HFD), syngenic EO771 cells were implanted into mammary glands, and tumour growth was monitored until sacrifice. Despite similar physical activity and food intake, the LT HFD group exhibited higher visceral adipose tissue mass and reduced skeletal muscle mass. In the tumour microenvironment, the LT HFD group showed decreased NK cells and TCD8+ cells, with a trend toward increased T regulatory cells, leading to a collapse of the T8/Treg ratio. Additionally, the LT HFD group displayed decreased tumour triglyceride content and altered enzyme activities indicative of oxidative stress. Prolonged exposure to HFD was associated with tumour growth despite elevated physical activity, promoting a tolerogenic tumour microenvironment. Future studies should explore inter-organ exchanges between tumour and tissues.

Do tight nosebands have an effect on the upper airways of horses?

BACKGROUND/OBJECTIVES: The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at events. In this context, very tight nosebands, which are intended to prevent the horse from opening its mouth, also attract a lot of attention. Various studies have evaluated the impact of tight nosebands on stress parameters, whereas the effect of tight nosebands on upper airway function is unknown. Therefore, the aim of the study was to use overground endoscopy to evaluate changes in pharyngeal and laryngeal function when a tight noseband is fitted. Moreover, the ridden horse pain ethogram (RHpE) was applied to investigate signs of discomfort (Dyson et al., 2018). STUDY DESIGN: A randomized, blinded, and prospective study was performed. METHODS: Sixteen warmblood horses consisting of twelve mares and four geldings with a mean age of 11.63 ± 3.53 years were ridden on 2 consecutive days with either loose or tight nosebands (two fingers or no space between bridge of the nose and noseband, respectively) and inserted endoscope in a random order. Videos were taken in a riding arena during a standardized exercise protocol involving beginner level tasks for 30 min in all gaits. For video analysis, freeze frames were prepared and analyzed at the beginning of the expiration phase. Pharyngeal diameter was measured using the pharynx-epiglottis ratio. Other findings (swallowing, pharyngeal collapse, soft palate movements, and secretion) were also evaluated. Moreover, the RHpE was applied. Descriptive statistics and generalized linear mixed effects models were used. Results with a p-value < 0.05 were considered statistically significant. RESULTS: While the pharynx-epiglottis ratio did not change significantly in horses ridden with loose versus tight nosebands, there was an increase in mean grade and total counts of parameters assessed in the pharyngeal region, for example, grade of secretion (1.5 [±SD 0.89] vs. 3.13 [±SD 0.96]; p = 0.0001), axial deviation of the aryepiglottic folds (0.29 [±SD 0.73] vs. 1.33 [±SD 1.44]; p = 0.01), and pharyngeal collapse (0.69 [±SD 0.87] vs. 1.88 [±SD 1.54]; p = 0.005) in horses ridden with tight nosebands. There was no RHpE score above 8 indicating musculoskeletal pain, but the RHpE scores were significantly higher in horses ridden with tight nosebands (p < 0.001). MAIN LIMITATIONS: Video quality was limited when horses showed large amounts of secretion. Another limitation was the small number of horses. CONCLUSIONS: Results add to the evidence obtained in other studies that tight nosebands do not only cause adverse reactions based on the RHpE score such as head behind the vertical or intense staring but also contribute to changes in the pharyngeal region, such as increased secretion and collapse of pharyngeal structures. This may provide further support for future decisions regarding regulations on nosebands.

The analysis of the skeletal muscle metabolism is crucial for designing optimal exercise paradigms in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results. METHODS: To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity. RESULTS: We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to ß-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations. CONCLUSION: The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients.

Exercise may improve lung immunity after surgical stress: Evidence from a nephrectomy model via a bioinformatic analysis.

Exercise offers numerous benefits to cancer patients and plays an essential role in postsurgical cancer rehabilitation. However, there is a lack of research examining the effects of exercise after the surgical stress of nephrectomy. To address this gap, we created an animal model that simulated patients who had undergone nephrectomy with or without an exercise intervention. Next, we performed a bioinformatic analysis based on the data generated by the RNA sequencing of the lung tissue sample. An overrepresentation analysis was conducted using two genome databases (Gene Ontology and Kyoto Encyclopedia of Genes and Genomes [KEGG]). A KEGG analysis of the exercise-treated nephrectomy mice revealed enrichment in immune-related pathways, particularly in the NF-κB and B cell-related pathways. The expression of CD79A and IGHD, which are responsible for B cell differentiation and proliferation, was upregulated in the nephrectomy mice. Differential gene expression was categorized as significantly upregulated or downregulated according to nephrectomy and exercise groups. Notably, we identified several gene expression reversals in the nephrectomy groups with exercise that were not found in the nephrectomy without exercise or control groups. Our preliminary results potentially reveal a genetic landscape for the underlying mechanisms of the effects of exercise on our nephrectomy model.

Adipose Kiss1 controls aerobic exercise-related adaptive responses in adipose tissue energy homeostasis.

Kisspeptin signaling regulates energy homeostasis. Adiposity is the principal source and receiver of peripheral Kisspeptin, and adipose Kiss1 metastasis suppressor (Kiss1) gene expression is stimulated by exercise. However, whether the adipose Kiss1 gene regulates energy homeostasis and plays a role in adaptive alterations during prolonged exercise remains unknown. Here, we investigated the role of Kiss1 role in mice and adipose tissues and the adaptive changes it induces after exercise, using adipose-specific Kiss1 knockout (Kiss1adipoq-/-) and adeno-associated virus-induced adipose tissue Kiss1-overexpressing (Kiss1adipoq over) mice. We found that adipose-derived kisspeptin signal regulates lipid and glucose homeostasis to maintain systemic energy homeostasis, but in a sex-dependent manner, with more pronounced metabolic changes in female mice. Kiss1 regulated adaptive alterations of genes and proteins in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OxPhos) pathways in female gWAT following prolonged aerobic exercise. We could further show that adipose Kiss1 deficiency leads to reduced peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α) protein content of soleus muscle and maximum oxygen uptake (VO2 max) of female mice after prolonged exercise. Therefore, adipose Kisspeptin may be a novel adipokine that increases organ sensitivity to glucose, lipids, and oxygen following exercise.

Exercise-induced muscle hormone "irisin" controls luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs.

Irisin is a hormone secreted by muscle in response to exercise. The irisin receptor (IrisinR) is a heterodimer of integrin alpha V (ITGAV) and integrin beta 5 (ITGB5) subunits. Since irisin may mediate some beneficial effects of exercise on animal reproduction, we tested the hypothesis that bovine gonadotrophs express IrisinR and irisin stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion by gonadotrophs. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of both ITGAV and ITGB5 in the anterior pituitary glands (APs) of post pubertal heifers and mouse gonadotroph cell line "LßT2." Western blotting was used to detect protein expression in bovine APs. Immunofluorescence microscopy, utilizing the same antibody, visualized IrisinR on the plasma membrane of majority of gonadotrophs. We prepared AP cells from healthy postpubertal heifers, cultured them for 3.5 d, and treated them with increasing concentrations (0, 0.01, 0.1, 1, or 10 nM) of irisin for 5 min before either no treatment or gonadotropin-releasing hormone (GnRH) stimulation. After 2 h, media were harvested for LH and FSH assays. Irisin (0.1-10 nM) stimulated basal LH and FSH secretion, and these stimulatory effects were inhibited by the extracellular signal-regulated kinase or SMAD pathway inhibitors. In the presence of GnRH, irisin at 0.01-1 nM stimulated LH and FSH secretion. A higher dose of irisin (10 nM), however, suppressed the GnRH-induced LH and FSH levels. In conclusion, bovine gonadotrophs expressed IrisinR, and irisin controlled LH and FSH secretion from bovine gonadotrophs.

Detraining after short-term exercise induces hyperphagia and obesity with fatty liver and brown adipose tissue whitening in young male OLETF rats.

This study examined the effects of exercise and detraining at a young age on fat accumulation in various organs. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF) rats were assigned to either the non-exercise sedentary (OLETF Sed) or exercise groups. The exercise group was subdivided into two groups: exercise between 4 and 12 weeks of age (OLETF Ex) and exercise between 4 and 6 weeks of age followed by non-exercise between 6 and 12 weeks of age (OLETF DT). Body weight was significantly lower in the OLETF Ex group than in the OLETF Sed group at 12 weeks of age. Fat accumulation in the epididymal white adipose tissue, liver, and brown adipose tissue was suppressed in the OLETF Ex group. During the exercise period, body weight and food intake in the OLETF DT group were significantly lower than those in the OLETF Sed group. However, food intake was significantly higher in the OLETF DT group than in the OLETF Sed group after exercise cessation, resulting in extreme obesity with fatty liver and brown adipose tissue whitening. Detraining after early-onset exercise promotes hyperphagia, causing extreme obesity. Overeating should be avoided during detraining periods in cases of exercise cessation at a young age.

Changes in muscle activation with graded surfaces during canter in Thoroughbred horses on a treadmill.

Understanding how muscle activity changes with different surface grades during canter is essential for developing training protocols in Thoroughbreds because canter is their primary gait in training and races. We measured the spatiotemporal parameters and the activation of 12 surface muscles in the leading limb side of 7 Thoroughbreds. Horses were equipped with hoof strain gauges and cantered at 10 m/s on a treadmill set to grades of -4%, 0%, 4%, and 8%, randomly, for 30 seconds each without a lead change. Integrated electromyography (iEMG) values during stance and swing phases were calculated and normalized to mean iEMG values during stride duration at 0% grade in each muscle. The iEMG values at each grade were compared using a generalized mixed model. Stride duration significantly decreased due to shorter swing duration on an 8% grade (P < 0.001) compared to all other grades, where no significant changes were observed. Compared to a 0% grade, the normalized iEMG values during the stance phase on an 8% grade in five muscles significantly increased (Musculus infraspinatus; +9%, M. longissimus dorsi (LD); +4%, M. gluteus medius (GM); +29%, M. biceps femoris; +47%, M. flexor digitorum lateralis; +16%). During the swing phase, the normalized iEMG values in six muscles significantly increased on an 8% grade compared to a 0% grade (M. splenius; +21%, M. triceps brachii; +54%, LD; +37%, GM; +24%, M. semitendinosus; +51%, M. extensor digitorum longus; +10%). No significant changes were observed in iEMG values on -4% and 4% grades compared to the 0% grade. Although +/- 4% grades had little effect on neuromuscular responses, 8% uphill canter reduced stride duration due to decreased swing duration and required increase of muscle activation during either stance and swing phase. Canter on an 8% grade might strengthen equine muscles to increase propulsive force and stride frequency.

Physical training minimizes immunological dysfunction, oxidative stress and tissue destruction on experimental periodontitis in rats.

The objective of this study is to investigate the effects of a moderate intensity physical training protocol, on alveolar bone morphology of rats submitted to ligature-induced periodontitis. Twenty-eight male Wistar rats were divided into four groups, considering the presence/absence of periodontitis and presence/absence of training. The training protocol was performed on a treadmill, 30 min/day, 5 days a week, for 4 weeks. In the experimental periodontal breakdown, with/without training, ligatures were placed on the lower first molars on the 14th day of the experiment, and were followed until the end of the protocol. At the end of the experiment, animals were euthanized and samples of plasma and mandibles were collected for immunoenzymatic evaluation of interleukins (IL)-1ß, IL-6, TNF-α and IL-10, evaluation of serum concentrations of C-reactive protein, analysis of lipid peroxidation (LPO) and reduced glutathione, histological and microtomographic analyses were performed. Physical training resulted in a reduced levels of IL-1ß, IL-6, TNF-α C-reactive protein and LPO and an increase in the levels of IL-10 in rats with periodontitis (p<0.05); a reduction in the inflammatory infiltrate and decreased fiber degradation was identified in histological analysis. Additionally, it was shown a decrease in vertical bone loss and an increase in the bone volume/trabecular volume ratio was identified in periodontitis+physical training group (p<0.05). Based on the results, the practice of frequent physical exercise, at moderate intensity, can contribute to the reduction of damage related to the disproportionate inflammatory response in periodontitis.

Exercise following joint distraction inhibits muscle wasting and delays the progression of post-traumatic osteoarthritis in rabbits by activating PGC-1α in skeletal muscle.

OBJECTIVE: Muscle wasting frequently occurs following joint trauma. Previous research has demonstrated that joint distraction in combination with treadmill exercise (TRE) can mitigate intra-articular inflammation and cartilage damage, consequently delaying the advancement of post-traumatic osteoarthritis (PTOA). However, the precise mechanism underlying this phenomenon remains unclear. Hence, the purpose of this study was to examine whether the mechanism by which TRE following joint distraction delays the progression of PTOA involves the activation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as its impact on muscle wasting. METHODS: Quadriceps samples were collected from patients with osteoarthritis (OA) and normal patients with distal femoral fractures, and the expression of PGC-1α was measured. The hinged external fixator was implanted in the rabbit PTOA model. One week after surgery, a PGC-1α agonist or inhibitor was administered for 4 weeks prior to TRE. Western blot analysis was performed to detect the expression of PGC-1α and Muscle atrophy gene 1 (Atrogin-1). We employed the enzyme-linked immunosorbent assay (ELISA) technique to examine pro-inflammatory factors. Additionally, we utilized quantitative real-time polymerase chain reaction (qRT-PCR) to analyze genes associated with cartilage regeneration. Synovial inflammation and cartilage damage were evaluated through hematoxylin-eosin staining. Furthermore, we employed Masson's trichrome staining and Alcian blue staining to analyze cartilage damage. RESULTS: The decreased expression of PGC-1α in skeletal muscle in patients with OA is correlated with the severity of OA. In the rabbit PTOA model, TRE following joint distraction inhibited the expressions of muscle wasting genes, including Atrogin-1 and muscle ring finger 1 (MuRF1), as well as inflammatory factors such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in skeletal muscle, potentially through the activation of PGC-1α. Concurrently, the production of IL-1ß, IL-6, TNF-α, nitric oxide (NO), and malondialdehyde (MDA) in the synovial fluid was down-regulated, while the expression of type II collagen (Col2a1), Aggrecan (AGN), SRY-box 9 (SOX9) in the cartilage, and superoxide dismutase (SOD) in the synovial fluid was up-regulated. Additionally, histological staining results demonstrated that TRE after joint distraction reduced cartilage degeneration, leading to a significant decrease in OARSI scores.TRE following joint distraction could activate PGC-1α, inhibit Atrogin-1 expression in skeletal muscle, and reduce C-telopeptides of type II collagen (CTX-II) in the blood compared to joint distraction alone. CONCLUSION: Following joint distraction, TRE might promote the activation of PGC-1α in skeletal muscle during PTOA progression to exert anti-inflammatory effects in skeletal muscle and joint cavity, thereby inhibiting muscle wasting and promoting cartilage regeneration, making it a potential therapeutic intervention for treating PTOA.

The activation of AMPK/PGC-1α/GLUT4 signaling pathway through early exercise improves mitochondrial function and mitigates ischemic brain damage.

Mitochondria play a crucial role in maintaining cellular energy supply and serve as a source of energy for repairing nerve damage following a stroke. Given that exercise has the potential to enhance energy metabolism, investigating the impact of exercise on mitochondrial function provides a plausible mechanism for stroke treatment. In our study, we established the middle cerebral artery occlusion (MCAO) model in Sprague-Dawley rats and implemented early exercise intervention. Neurological severity scores, beam-walking test score, and weight were used to evaluate neurological function. The volume of cerebral infarction was measured by MRI. Nerve cell apoptosis was detected by TUNEL staining. Mitochondrial morphology and structure were detected by mitochondrial electron microscopy. Mitochondrial function was assessed using membrane potential and ATP measurements. Western blotting was used to detect the protein expression of AMPK/PGC-1α/GLUT4. Through the above experiments, we found that early exercise improved neurological function in rats after MCAO, reduced cerebral infarction volume and neuronal apoptosis, promoted the recovery of mitochondrial morphology and function. We further examined the protein expression of AMPK/PGC-1α/GLUT4 signaling pathway and confirmed that early exercise was able to increase its expression. Therefore, we suggest that early exercise initiated the AMPK/PGC-1α/GLUT4 signaling pathway, restoring mitochondrial function and augmenting energy supply. This, in turn, effectively improved both nerve and body function in rats following ischemic stroke.

Effects of astaxanthin on gut microbiota of polo ponies during deconditioning and reconditioning periods.

To determine the effects of astaxanthin (ASTX) supplementation on the equine gut microbiota during a deconditioning-reconditioning cycle, 12 polo ponies were assigned to a control (CON; n = 6) or supplemented (ASTX; 75 mg ASTX daily orally; n = 6) group. All horses underwent a 16-week deconditioning period, with no forced exercise, followed by a 16-week reconditioning program where physical activity gradually increased. Fecal samples were obtained at the beginning of the study (Baseline), after deconditioning (PostDecon), after reconditioning (PostRecon), and 16 weeks after the cessation of ASTX supplementation (Washout). Following DNA extraction from fecal samples, v4 of 16S was amplified and sequenced to determine operational taxonomic unit tables and α-diversity and ß-diversity indices. The total number of observed species was greater at Baseline than PostDecon, PostRecon, and Washout (p ≤ 0.02). A main effect of ASTX (p = 0.01) and timepoint (p = 0.01) was observed on ß-diversity, yet the variability of timepoint was greater (13%) than ASTX (6%), indicating a greater effect of timepoint than ASTX. Deconditioning and reconditioning periods affected the abundance of the Bacteroidetes and Fibrobacteres phyla. Physical activity and ASTX supplementation affect the equine gut microbiome, yet conditioning status may have a greater impact.

Interval training suppresses nod-like receptor protein 3 inflammasome activation to improve cardiac function in myocardial infarction rats by hindering the activation of the transforming growth factor-ß1 pathway.

OBJECTIVE: Myocardial infarction (MI) -induced cardiac dysfunction can be attenuated by aerobic exercises. This study explored the mechanism of interval training (IT) regulating cardiac function in MI rats, providing some theoretical basis for clarifying MI pathogenesis and new ideas for clinically treating MI. METHODS: Rats were subjected to MI modeling, IT intervention, and treatments of the Transforming growth factor-ß1 (TGF-ß1) pathway or the nod-like receptor protein 3 (NLRP3) activators. Cardiac function and hemodynamic indicator alterations were observed. Myocardial pathological damage and fibrosis, reactive oxygen species (ROS) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, MDA content, inflammasome-associated protein levels, and inflammatory factor levels were assessed. The binding between TGF-ß1 and receptor was detected. RESULTS: MI rats exhibited decreased left ventricle ejection fraction (LVEF), left ventricle fractional shortening  (LVFS), left ventricular systolic pressure  (LVSP), positive and negative derivates max/min (dP/dt max/min) and increased left ventricular end-systolic pressure (LVEDP), a large number of scar areas in myocardium, disordered cell arrangement and extensive fibrotic lesions, increased TGF-ß1 and receptor binding, elevated ROS level and MDA content and weakened SOD, CAT and GSH-Px activities, and up-regulated NLRP3, apoptosis-associated speck-like protein containing a CARD  (ASC) and cleaved-caspase-1 levels, while IT intervention caused ameliorated cardiac function. IT inactivated the TGF-ß1 pathway to decrease oxidative stress in myocardial tissues of MI rats and inhibit NLRP3 inflammasome activation. Activating NLRP3 partially reversed IT-mediated improvement on cardiac function in MI rats. CONCLUSION: IT diminished oxidative stress in myocardial tissues and suppressed NLRP3 inflammasome activation via inactivating the TGF-ß1 pathway, thus improving the cardiac function of MI rats.