Combined physical exercise re-synchronizes expression of Bmal1 and REV-ERBα and up-regulates apoptosis and metabolism in the prostate during aging.

BACKGROUND: Aging increases the prevalence of prostate cancer. The circadian clock coordinates metabolism, cell cycle, and tumor suppressor p53. Although physical exercise has several effects on preventing prostate diseases, its effect on regulating genes and proteins of the circadian rhythm of the prostate needs to be better evaluated. The present study verified expression of REV-ERBα (Nr1d1), Bmal1, apoptosis, tumor suppressors, energetic metabolism markers, and androgen receptors in the prostatic microenvironment in 18-month-old mice submitted to combined physical training. METHODS: C57BL/6 J mice were divided into 2 groups: 6 months-old (n = 10) and 18 months-old, (n = 20). The 18-month-old animals were divided into 2 subgroups: sedentary (n = 10, 18 m Sed) and submitted to combined physical training (n = 10, 18 m TR). Combined physical training protocol was performed by running on the treadmill (40-60 % of incremental load test) and climbing strength training (40-50 % of maximum repetition test), consisting of 5×/week (3 days aerobic and 2 days strength) for 3 weeks. The prostate was prepared for Western blot and RT-qPCR analysis, and the plasm was prepared for the biochemistry analysis. RESULTS: Combined physical exercise during aging led to increased levels of Bmal1 and decreased levels of REV-ERBα in the prostate. These results were accompanied by a reduction in the AMPK/SIRT1/PGC-1α proteins and an increase in the PI3K/AKT and p53/PTEN/caspase 3 pathways, promoting apoptotic potential. CONCLUSION: These findings suggest that strength and aerobic physical exercise may be preventive in the development of preneoplastic molecular alterations and age-related features by re-synchronizes Bmal1 and REV-ERBα in prostatic tissues.

Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake.

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.

Glycogen Kinetics of Wistar Rats: Different Exercise Intensities and Tissue Analyzed Influence.

The aim of this study is to verify the influence of the intensity on muscle and hepatic glycogen depletion and recovery kinetics of Wistar rats, submitted to three acute training sessions with equalized loads. 81 male Wistar rats performed an incremental test to determine maximal running speed (MRS) and divided into 4 groups: baseline group (Control; n = 9); low intensity training session (GZ1; n = 24; 48 minutes at 50% of MRS); moderate intensity group (GZ2; n = 24; 32 minutes at 75% of MRS) and high intensity group (GZ3; n = 24; 5x5 minutes and 20 seconds at 90% of MRS). Immediately after the sessions and after 6, 12 and 24 hours, 6 animals from each subgroup were euthanized for glycogen quantification in soleus and EDL muscles and liver. A Two-Way ANOVA and the Fisher's Post-hoc test was used (p < 0.05). Glycogen supercompensation occurred between 6 and 12 hours after exercise in muscle tissue and 24 after exercise in the liver. The muscle and hepatic glycogen depletion and recovery kinetics are not modulated by exercise intensity since the load was equalized, but effects were distinct in different tissues. Hepatic glycogenolysis and muscle glycogen synthesis processes seem to run in parallel.

Role of TLR4 in physical exercise and cardiovascular diseases.

Cardiovascular diseases are a leading cause of death for adults worldwide. Published articles have shown that toll-like receptor 4 (TLR4), a member of the toll-like receptor (TLR) family, is involved in several cardiovascular diseases and can be modulated by physical exercise. TLR4 is the most expressed TLR in cardiac tissue and is an essential mediator of the inflammatory and apoptosis processes in the heart, playing a pivotal role in the development of cardiovascular diseases. Physical exercise is recognized as a non-pharmacological strategy for the prevention and treatment of these diseases. In addition, physical exercise can modulate the TLR4 in the mice heart, and its absence attenuates apoptosis, endoplasmic reticulum stress, and inflammation. However, the relationship between TLR4 and physical exercise-induced cardiac adaptations has barely been explored. Thus, the objective of this brief review was to discuss studies describing how TLR4 influences cardiac responses to physical exercise and present a link between these responses and cardiovascular diseases, showing physical activity improves the cardiac function of individuals with cardiovascular diseases through the TLR4 modulation.

Short-Term Combined Exercise Improves Inflammatory Profile in the Retina of Obese Mice.

Excess of adipose tissue increases the concentration of proinflammatory cytokines, triggering a subclinical inflammatory condition. This inflammatory profile contributes to retina damage, which can lead to retinal dysfunction and reduced vision. Regularly practicing both aerobic and strength exercises is well known for promoting anti-inflammatory effects on different organs in the peripheral and central regions. However, the effects of combined physical exercise (CPE; strength + aerobic) on the inflammatory process in the retina tissue are not yet known. This study aimed to investigate the effects of CPE on the inflammatory profile of the retina in obese mice. Swiss mice were distributed into control, sedentary obese, and trained obese groups. The trained obese group was subjected to short-term CPE, 1 h/day, for 7 days. The CPE was composed of aerobic and strength exercises in the same exercise session. The strength exercise protocol consisted of 10 climbing series, with 12 ± 1 dynamic climbing movements at 70% of the maximum voluntary carrying capacity (MVCC), and the aerobic exercise protocol consisted of 30 min of treadmill running, with an intensity of 75% of the exhaust velocity. Subsequently, the retina was excised and analyzed by Western blot. Obese animals presented impairment on glucose homeostasis and elevated levels of proinflammatory proteins in the serum and retina; however, CPE was effective in reversing these parameters, independently of changes in body adiposity. Therefore, for the first time, we have shown that short-term CPE can be an important strategy to treat an inflammatory profile in the retina.

The reversal effect of physical exercise on aging-related increases in APPL2 content in skeletal muscle.

AIMS: The aim of this study was to evaluate the effects of aging on intracellular adiponectin signaling and the possible therapeutic effect of physical exercise. MAIN METHODS: Fischer 344 rats were distributed in the following groups: Young (3 months old); Sedentary Old (Old, 27 months old); and Old Exercised (Old-Exe, 27 months old), which were subjected to a short-term exercise training protocol. KEY FINDINGS: The results showed that the old rats presented glucose intolerance without increased adiposity. However, short-term exercise training reversed this disorder, which was associated with a decrease in the pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif (APPL) isoform 2 (APPL2) content. The APPL isoform 1 (APPL1) and TRB3 (Tribbles homolog 3) contents were not altered. Akt phosphorylation was only increased in the old exercised rats. There was a reduction in the content of adiponectin receptor 1 in the old rats. SIGNIFICANCE: The short-term exercise training protocol was able to decrease APPL2 content in the skeletal muscle, which was accompanied by an improvement in the glucose tolerance of the old Fischer 344 rats. These findings provide new evidence supporting the role of physical exercise as a non-pharmacological therapeutic intervention to attenuate age-related deficits.

Excessive training is associated with endoplasmic reticulum stress but not apoptosis in the hypothalamus of mice.

Downhill running-based overtraining model increases the hypothalamic levels of IL-1ß, TNF-α, SOCS3, and pSAPK-JNK. The aim of the present study was to verify the effects of 3 overtraining protocols on the levels of BiP, pIRE-1 (Ser724), pPERK (Thr981), pelF2α (Ser52), ATF-6, GRP-94, caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) proteins in the mouse hypothalamus. The mice were randomized into the control, overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR) groups. After the overtraining protocols (i.e., at the end of week 8), hypothalamus was removed and used for immunoblotting. The OTR/down group exhibited increased levels of all of the analyzed endoplasmic reticulum stress markers in the hypothalamus at the end of week 8. The OTR/up and OTR groups exhibited increased levels of BiP, pIRE-1 (Ser724), and pPERK (Thr981) in the hypothalamus at the end of week 8. There were no significant differences in the levels of caspase 4, caspase 12, pAKT (Ser473), pmTOR (Ser2448), and pAMPK (Thr172) between the experimental groups at the end of week 8. In conclusion, the 3 overtraining protocols increased the endoplasmic reticulum stress at the end of week 8.