Obesity-dependent molecular alterations in fatal COVID-19: A retrospective postmortem study of metabolomic profile of adipose tissue.

We investigated the effects of obesity on metabolic, inflammatory, and oxidative stress parameters in the adipose tissue of patients with fatal COVID-19. Postmortem biopsies of subcutaneous adipose tissue were obtained from 25 unvaccinated inpatients who passed from COVID-19, stratified as nonobese (N-OB; body mass index [BMI], 26.5 ± 2.3 kg m-2) or obese (OB BMI 34.2 ± 5.1 kg m-2). Univariate and multivariate analyses revealed that body composition was responsible for most of the variations detected in the metabolome, with greater dispersion observed in the OB group. Fifteen metabolites were major segregation factors. Results from the OB group showed higher levels of creatinine, myo-inositol, O-acetylcholine, and succinate, and lower levels of sarcosine. The N-OB group showed lower levels of glutathione peroxidase activity, as well as higher content of IL-6 and adiponectin. We revealed significant changes in the metabolomic profile of the adipose tissue in fatal COVID-19 cases, with high adiposity playing a key role in these observed variations. These findings highlight the potential involvement of metabolic and inflammatory pathways, possibly dependent on hypoxia, shedding light on the impact of obesity on disease pathogenesis and suggesting avenues for further research and possible therapeutic targets.

Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit- COVID study.

Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 ± 43.10 days of diagnosis; age: 29.4 (21.9- 34.9) years; BMI: 25.5 ± 4.3 kg m2 n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 ± 4.7 kg m2; n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE2 (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8+ T cells (p adj = 0.014), whereas CD4+T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-α clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-α and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.

Relationship of Testosterone, LH, Estradiol, IGF-1, and SHBG with Physical Performance of Master Athletes.

Purpose: The aim of this study was to investigate and compare the levels of luteinizing hormone (LH), testosterone (T), estradiol (ES), sex hormone-binding globulin (SHBG), and insulin-like growth factor 1 (IGF-1) in master sprint (MS) and master endurance (ME) athletes. Additionally, the possible associations between these hormones, body composition, and lipid profile with athletic performance (% of performance in relation to the current world record) were analyzed. Materials and Methods: The participants were all men: (i) 34 MS (51.0 ± 6.8 years); and (ii) 32 ME (51.7 ± 9.4 years). Student's t-tests for independent samples were performed to compare all variables between groups. Results: MS had a significantly higher (p = .008) average IGF-1 (154.78 ± 29.85 ng/mL) when compared to ME (129.92 ± 25.48 ng/mL). Performance was significantly correlated with IGF-1 (r = 0.424). The MS group had a moderately lower body fat than ME athletes (MS 12.54 ± 4.07 vs. ME 14.60 ± 4.12; p = .078; d = 0.503). Conclusions: Thus, strength/power training exercise/sport seems to be more beneficial for obtaining a higher IGF-1 compared to aerobic/distance exercise/sport. In addition, LH, T, ES, and SHBG were similar between the two groups of athletes and were comparable to the reference values of younger adults.

Exercise training-induced changes in immunometabolic markers in youth badminton athletes.

The aim of this study was to investigate the metabolic and inflammatory fluctuations in two seasonal phases of badminton training, and the ability of youth badminton athletes to respond to an inflammatory challenge given by acute exercise on these markers. Thirteen youth badminton athletes who participated in national and international competitions were recruited. Metabolic and cytokine profile were measured at rest and in response to a maximal exercise intermittent test, in the pre- and final phases of a badminton annual season. At rest, glucose (-7.58 mg/dL; p = 0.045) and HDL-cholesterol (HDL-c) (-26.87 mg/dL; p < 0.0001) decreased at final-season. The variation of HDL-c in response to a maximal exercise test increased at final-season in comparison to pre-season (+ 10.20 mg/dL p = 0.042). Similarly, delta changes of IL-10 (+ 3.41 pg/ml; p = 0.047) and IL-1Ra (+ 141.3 pg/ml; p = 0.031) were greater at final-season. In addition, a significantly greater variation of the anti-inflammatory IL-10/IL-17 ratio was observed at final-season (+ 0.37; p = 0.010). In conclusion, our results showed a major responsivity of IL-10 and IL-1Ra to a maximal exercise even at the end of an entire season. The major responsivity of these cytokines at this time point suggests a more effective acute inflammatory response in youth badminton athletes. Therefore, the results of this study may be applied by coaches, trainers and sport nutritionist for proper training management.

Feeding Pattern, Circadian Rhythm, and Immune Function: What do we know about?

Feeding pattern is related to health status or chronic diseases, and this depends on the individual's eating habits. Feeding organized with the right time to start and end during the day, promotes an internal biological rhythm, favoring molecular synchronization of the clock genes, which impose an effect on metabolism and immune cells, creating a physiological response related to a healthy profile. On the other hand, a feeding pattern disorganized, without the right time to start and end eating during the day, might lead to nonsynchronization of the clock genes, a disruption condition, which is related to chronic diseases, such as obesity and diabetes type 2. A strategy that should be adopted to favor molecular synchronization is time-restricted eating (TRE), which can organize the initial and end of the eating patterns during the day. Our review points out some cues that suggest TRE as an efficient strategy for healthy profile and can be a good intervention for the treatment of chronic diseases.

Potential Anticarcinogenic Effects From Plasma of Older Adults After Exercise Training: An Exploratory Study.

Aim: To evaluate the impact of exercise training plasma on in vitro prostate cancer cell viability and proliferation. Methods: PC3 prostate cancer cells were incubated with plasma obtained from young men with high and low physical fitness (PF) (high PF, n = 5; low PF, n = 5) and with the plasma collected from institutionalized older adults (n = 8) before and after multimodal exercise training. Cell viability and proliferation, mitochondria membrane polarization, reactive oxygen species (ROS) generation, and apoptosis were evaluated after the cell treatment with plasma. Systemic cytokines were evaluated in the plasma of institutionalized older adults submitted to an exercise training protocol. Results: Plasma from high-PF men lowers both cell viability and proliferation after the incubation time. PC3 cells also presented lower cell viability and diminished rates of cell proliferation after the incubation with post-training plasma samples of the older adults. The incubation of PC3 cells with post-training plasma of older adults depolarized the mitochondrial membrane potential and increased mitochondrial reactive oxygen species production. Post-training plasma did not change apoptosis or necrosis rates in the PC3 cell line. Multimodal exercise training increased the plasma levels of IL-2, IL-10, IFN-α, and FGF-1 and decreased TNF-α concentrations in institutionalized older adults. Conclusion: Adaptations in blood factors of institutionalized older adults may alter cell viability and proliferation by targeting mitochondrial ROS in a prostate cancer cell line.

Immunometabolism-fit: How exercise and training can modify T cell and macrophage metabolism in health and disease.

BACKGROUND: The term immunometabolism describes cellular and molecular metabolic processes that control the immune system and the associated immune responses. Acute exercise and regular physical activity have a substantial influence on the metabolism and the immune system, so that both processes are closely associated and influence each other bidirectionally. SCOPE OF REVIEW: We limit the review here to focus on metabolic phenotypes and metabolic plasticity of T cells and macrophages to describe the complex role of acute exercise stress and regular physical activity on these cell types. The metabolic and immunological consequences of the social problem of inactivity and how, conversely, an active lifestyle can break this vicious circle, are then described. Finally, these aspects are evaluated against the background of an aging society. MAJOR CONCLUSIONS: T cells and macrophages show high sensitivity to changes in their metabolic environment, which indirectly or directly affects their central functions. Physical activity and sedentary behaviour have an important influence on metabolic status, thereby modifying immune cell phenotypes and influencing immunological plasticity. A detailed understanding of the interactions between acute and chronic physical activity, sedentary behaviour, and the metabolic status of immune cells, can help to target the dysregulated immune system of people who live in a much too inactive society.

High-intensity intermittent exercise induces a potential anti-inflammatory response in healthy women across the menstrual cycle.

AIM: This observational study aimed to examine cytokine responses to high-intensity intermittent exercise (HIIE) in the follicular and luteal phases of the menstrual cycle. METHODS: Fourteen healthy women (24 ± 2 years; body mass index [BMI]: 22.8 ± 1.9 kg⋅m2; maximal oxygen consumption [V̇O2max]: 41.5 ± 4.1 mL⋅kg-1⋅min-1) with regular menstrual cycles were randomly assigned to 4 experimental sessions, 2 during the follicular and 2 during the luteal phase. V̇O2max and maximum aerobic velocity (MAV) were determined prior to the experimental sessions through a graded exercise test during both follicular and luteal phases. Seventy-two hours after having completed the graded exercise test, all participants performed a HIIE session (10 x 1-min sprints with 1 min of rest) at 90% of their MAV. Serum concentrations of TNF-α, IL-6, IL-10 and IL-17 were measured before (Pre), immediately after (Post) and 1 h after (1 h Post) the HIIE sessions. RESULTS: Pre-exercise concentrations of TNF-α and IL-10 were significantly higher in the luteal phase compared to the follicular phase (P < 0.01), with no differences seen on IL-6 and IL-17, demonstrating an altered inflammatory status in the luteal phase. There was a significant interaction for IL-10 concentration (P < 0.01) with reductions in both luteal (Pre vs Post, 95 %CI: 1.086 to 6.156; and Pre vs 1 h Post, 95 %CI: 1.720 to 9.013, P < 0.01) and follicular phase (Pre vs 1 h Post, 95 %CI: 0.502 to 7.842, P < 0.05). Despite no significant phase × time interaction for TNF-α concentration, its concentration at 1 h Post was significantly lower compared to Pre in the luteal phase analysis (Pre vs 1 h Post, 95 %CI: 0.71 to 14.06; P < 0.05). These results are in agreement with IL-10 responses, highlighting a reduction on the inflammatory status after exercise. CONCLUSION: Mostly during the luteal phase, high-intensity intermittent exercise modulates cytokine responses, thus impacting exercise recovery. In this scenario, high-intensity intermittent exercise emerges as a non-pharmacology strategy to regulate inflammatory responses on healthy women who were affected by an inflammatory state given their menstrual cycle.

Role of Body Mass and Physical Activity in Autonomic Function Modulation on Post-COVID-19 Condition: An Observational Subanalysis of Fit-COVID Study.

The harmful effects of coronavirus disease 2019 (COVID-19) can reach the autonomic nervous system (ANS) and endothelial function. Therefore, the detrimental multiorgan effects of COVID-19 could be induced by deregulations in ANS that may persist after the acute SARS-CoV-2 infection. Additionally, investigating the differences in ANS response in overweight/obese, and physically inactive participants who had COVID-19 compared to those who did not have the disease is necessary. The aim of the study was to analyze the autonomic function of young adults after mild-to-moderate infection with SARS-CoV-2 and to assess whether body mass index (BMI) and levels of physical activity modulates autonomic function in participants with and without COVID-19. Patients previously infected with SARS-CoV-2 and healthy controls were recruited for this cross-sectional observational study. A general anamnesis was taken, and BMI and physical activity levels were assessed. The ANS was evaluated through heart rate variability. A total of 57 subjects were evaluated. Sympathetic nervous system activity in the post-COVID-19 group was increased (stress index; p = 0.0273). They also presented lower values of parasympathetic activity (p < 0.05). Overweight/obese subjects in the post-COVID-19 group presented significantly lower parasympathetic activity and reduced global variability compared to non-obese in control group (p < 0.05). Physically inactive subjects in the post-COVID-19 group presented significantly higher sympathetic activity than active subjects in the control group. Parasympathetic activity was significantly increased in physically active subjects in the control group compared to the physically inactive post-COVID-19 group (p < 0.05). COVID-19 promotes changes in the ANS of young adults, and these changes are modulated by overweight/obesity and physical activity levels.

Modulatory Effects of Physical Activity Levels on Immune Responses and General Clinical Functions in Adult Patients with Mild to Moderate SARS-CoV-2 Infections-A Protocol for an Observational Prospective Follow-Up Investigation: Fit-COVID-19 Study.

Background: This proposal aims to explain some of the gaps in scientific knowledge on the natural history of coronavirus disease (COVID-19), with a specific focus on immune, inflammatory, and metabolic markers, in parallel with temporal assessment of clinical and mental health in patients with COVID-19. The study will explore the temporal modulatory effects of physical activity and body composition on individual trajectories. This approach will provide a better understanding of the survival mechanisms provided by the immunomodulatory role of physical fitness. Methods: We will conduct a prospective observational cohort study including adult patients previously infected with the SARS-CoV-2 virus who have expressed a mild to moderate COVID-19 infection. Procedures will be conducted for all participants at baseline, six weeks after vaccination, and again at 12 months. At each visit, a venous blood sample will be collected for immune phenotypic characterization and biochemistry assays (inflammatory and metabolic parameters). Also, body composition, physical activity level, cardiovascular and pulmonary function, peripheral and respiratory muscle strength, functional exercise capacity, and mental health will be evaluated. Using the baseline information, participants will be grouped based on physical activity levels (sedentary versus active), body composition (normal weight versus overweight or obese), and SARS-CoV-2 status (positive versus negative). A sub-study will provide mechanistic evidence using an in-vitro assay based on well-trained individuals and age-matched sedentary controls who are negative for SARS-CoV-2 infection. Whole blood will be stimulated using recombinant human coronavirus to determine the cytokine profile. Peripheral blood mononuclear cells (PBMCs) from healthy well-trained participants will be collected and treated with homologous serum (from the main study; samples collected before and after the vaccine) and recombinant coronavirus (inactive virus). The metabolism of PBMCs will be analyzed using Respirometry (Seahorse). Data will be analyzed using multilevel repeated-measures ANOVA. Conclusions: The data generated will help us answer three main questions: (1) Does the innate immune system of physically active individuals respond better to viral infections compared with that of sedentary people? (2) which functional and metabolic mechanisms explain the differences in responses in participants with different physical fitness levels? and (3) do these mechanisms have long-term positive modulatory effects on mental and cardiovascular health? Trial registration number: Brazilian Registry of Clinical Trials: RBR-5dqvkv3. Registered on 21 September 2021.

COVID-19 Outcome Relates With Circulating BDNF, According to Patient Adiposity and Age.

Background and Aims: We evaluated adipose tissue-derived hormones, body composition, serum metabolic profile, levels of brain-derived neurotrophic factor (BDNF), and the association of these parameters with the clinical outcome in patients with COVID-19. We sought to examine whether obesity, sex, and age influence the adipose tissue endocrine response to the disease. Methods: This prospective study investigated 145 hospitalized patients with COVID-19. Patients were categorized based on their body mass index (BMI), sex and age, and were also classified regarding their outcome after hospitalization as: (a) Non-ICU: patients hospitalized who did not receive intensive care; (b) ICU-survivor: patients admitted to the intensive care unit and discharged; (c) ICU-death: patients who died. Blood samples were collected by the hospital staff between the first and third day of hospitalization. Serum leptin, adiponectin and BDNF concentrations, triglycerides, total cholesterol and cholesterol fractions were performed following the manufacturer's guidelines. Results: We demonstrate that BDNF levels predict intensive care (IC) need (p < 0.01). This association was found to be stronger in patients >60y (p = 0.026). Neither leptin nor adiponectin concentration was associated with IC requirement or with patient's outcome, while the BDNF/adiponectin ratio was closely associated with worsened outcomes (p < 0.01). BDNF concentration was similar between sexes, however tended to be lower in male patients (p = 0.023). In older patients, BDNF concentration was lower than that of younger patients (p = 0.020). These age and sex-specific differences should be considered when employing these potential markers for prognosis assessment. While appetite and body composition regulating hormones secreted by the white adipose tissue are not reliable predictors of disease severity, the ratio BDNF/adiponectin was indicative of patient status. Conclusion: Thus, we propose that serum BDNF content and BDNF/adiponectin ratio may serve as tools predicting worsened prognosis in COVID-19, especially for male patients.

Improvement in the anti-inflammatory profile with lifelong physical exercise is related to clock genes expression in effector-memory CD4+ T cells in master athletes.

PURPOSE: Ageing is associated with alterations in the immune system as well as with alterations of the circadian rhythm. Immune cells show rhythmicity in execution of their tasks. Chronic inflammation (inflammaging), which is observed in the elderly, is mitigated by lifelong exercise. The aimed this study was to determine the acute effect of a maximal exercise test on clock genes, regulatory proteins and cytokine expression, and evaluate the effect of lifelong exercise on the expression of clock genes in subpopulations of effector-memory (EM) CD4+ and CD8+T cells and the association of these processes with the inflammatory profile. Therefore, this study aimed to investigate the expression of clock genes in subpopulations of effector memory (EM) CD4+ and CD8+ T cells in master athletes and healthy controls and further associate them with systemic inflammatory responses to acute exercise. METHODS: The study population comprised national and international master athletes (n = 18) involved in three sports (athletics, swimming and judo). The control group (n = 8) comprised untrained healthy volunteers who had not participated in any regular and competitive physical exercise in the past 20 years. Anthropometric measurements and blood samples were taken before (Pre), 10 min after (Post) and 1 h after (1 h Post) a maximal cycle ergometer test for the determination of maximum oxygen consumption (VO2 max). The subpopulations of EM CD4+ and CD8+ T cells were purified using fluorescenceactivated cell sorting. RNA extraction of clock genes (CLOCK, BMAL1, PER1, PER2, CRY1, CRY2, REV-ERBα, REV-ERBß, RORa, RORb and RORc) in EM CD4+ and EM CD8+ T cells as well as regulatory proteins (IL-4, IFN-γ, Tbx21, PD-1, Ki67, NF-kB, p53 and p21) in EM CD4+ T cells was performed. The serum concentration of cytokines (IL-8, IL-10, IL-12p70 and IL-17A) was measured. RESULTS: The master athletes showed better physiological parameters than the untrained healthy controls (P < 0.05). The levels of cytokines increased in master athletes at Post compared with those at Pre. The IL-8 level was higher at 1 h Post, whereas the IL-10 and IL-12p70 levels returned to baseline. There was no change in IL-17A levels (P < 0.05). The clock genes were modulated differently in CD4+ T cells after an acute session of exercise in a training status-dependent manner. CONCLUSION: The synchronization of clock genes, immune function and ageing presents new dimensions with interesting challenges. Lifelong athletes showed modified expression patterns of clock genes and cytokine production associated with the physical fitness level. Moreover, the acute bout of exercise altered the clock machinery mainly in CD4+ T cells; however, the clock gene expressions induced by acute exercise were different between the master athletes and control group.

Immunometabolic responses according to physical fitness status and lifelong exercise during aging: New roads for exercise immunology.

Molecules such as cytokines, energetic substrates, and hormones found in the immune cell environment, especially lymphocytes and monocytes, are crucial for directing energy metabolism. In turn, changes in energy metabolism occur in a synchronized manner with the activation of certain signaling pathways, thereby this crosstalk is responsible for determining the functionality of immune cells. The immunometabolism field has grown over time and that is becoming increasingly promising in several populations; here we discuss the mechanisms involved in sedentary and physically active middle-aged individuals and master athletes. In this context, this review shows that the physical activity status and lifelong exercise seems to be good strategies for the promotion of metabolic and functional adaptations in T lymphocytes and monocytes, counteracting inflammatory environments caused by expanded adipose tissue and sedentary behavior, as well as delaying the immunosenescence caused by aging.

Taurine supplementation reduces myeloperoxidase and matrix-metalloproteinase-9 levels and improves the effects of exercise in cognition and physical fitness in older women.

Immunosenescence contributes to cognitive impairment and neurodegeneration, and those conditions could be attenuated by non-pharmacological anti-inflammatory strategies, such as exercise and supplementation with the amino acid taurine. Since taurine body content decreases with aging, we investigated the effects of supplementation (alone and combined with exercise) on oxidative stress, extracellular matrix degradation, white blood cells, neurotrophins, cognition and physical fitness of elderly women. Forty-eight women (83.58 ± 6.98 years) were enrolled into exercise training only (EO: n = 13), taurine supplementation (TS: n = 12), exercise training + taurine supplementation (ETTS: n = 11), and control group (CG: n = 12). All interventions lasted 14 weeks. Exercise was applied twice a week, and taurine was given once a day (1.5 g). Data collection occurred before and after interventions with the determination of myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9), brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) levels, and white blood cell counts (WBC). Montreal cognitive assessment (MoCA) and physical fitness tests were also evaluated. Concentration of MPO and MMP-9 decreased after intervention in TS (p < 0.05). No effect of time or time × group was observed for WBC parameters; however, univariate analysis showed a significant decrease in lymphocytes for TS, while an increase in monocytes occurred in the CG (p < 0.05). MoCA scores decreased over time in the CG (p < 0.05). Improvements in physical fitness occurred in ETTS (better agility and aerobic capacity), mostly likely due to exercise and boosted by taurine supplementation. No changes in BDNF levels were observed (p > 0.05), while NGF concentration were undetectable in almost subjects. Exercise together with taurine supplementation appears to be a valuable strategy to enhance health-related outcomes in older persons.

Effects of short-term physical training on the interleukin-15 signalling pathway and glucose tolerance in aged rats.

PURPOSE: Interleukin-15 (IL-15) is a myokine that has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. However, the evidence suggesting a role for IL-15 in improving whole-body insulin sensitivity and decreasing adiposity comes mainly from studies using supraphysiological levels of this cytokine. This study examined the effect of a short-term exercise training protocol on the protein content of IL-15, it's signaling pathway, and glucose tolerance in aged rats. METHODS: Fourteen Wistar rats were divided into Young Sedentary (Young, n = 4); Old Sedentary (Old, n = 5); Old Exercise (Old.Exe, n = 5) groups. The animals from the exercised group were submitted to a short-term physical exercise protocol for five days. At the end of physical training and after 16 h of the last exercise session, the animals were euthanized, and tissue collection was done. RESULTS: Physical exercise decreased epididymal and mesenteric fat mass and promoted positive effects on glucose tolerance and insulin sensitivity. Muscle IL-15 protein levels were not changed following the short-term physical exercise training with no alterations in the post-exercise IL-15-JAK/STAT signaling pathway. We found a tendency to increased HIF1α and a significant increase in its regulator, PHD2, in the skeletal muscle after exercise. CONCLUSION: The elderly rats submitted to short-term aerobic physical training did not present skeletal muscle alteration in the protein content of the IL-15 and IL-15-JAK/STAT signaling pathway. However, short-term aerobic physical training was able to modulate the expression of HIF1α and its regulator PHD2, suggesting an essential role of these proteins in improving post-exercise glucose tolerance and insulin sensitivity in elderly rats.

Upper respiratory symptoms (URS) and salivary responses across a season in youth soccer players: A useful and non-invasive approach associated to URS susceptibility and occurrence in young athletes.

This study examined the effect of a competitive season on salivary responses [cortisol (sC), testosterone (sT), Testosterone/Cortisol ratio (sT/C), Immunoglobulin A (sIgA), sIgA secretion rate (srIgA), alpha-amylase (sAA)] and upper respiratory symptoms (URS) occurrence in three teams of male soccer players (Under-15, Under-17 and Under-19 yrs.). Training and competition volumes, salivary biomarkers and URS were determined monthly. No differences were found for monthly training volume between teams. Incidence of URS was higher for the U15 (44.9% of the total cases). Higher sT and srIgA were observed for the U19, lower sC were found for the U17 and sAA showed higher values for the U15 throughout the season. In the U15, significant difference (p = .023) was found for sIgA concentration with higher concentration values in January compared to December (-42.7%; p = .008) and the sT showed seasonal variation (p < .001) with the highest value in January significantly different from October (-40.2%; p = .035), November (-38.5%; p = 0.022) and December (-51.6%; p = .008). The U19 presented an increase in sC in March compared to February (-66.1%, p = .018), sT/C were higher in February compared to March (-58.1%; p = .022) and sAA increased in March compared to September (-20.5%; p = .037). Negative correlations, controlled for age group, were found between URS occurrence and srIgA (r = -0.170, p = .001), sAA (r = -0.179, p = .001) and sT (r = -0.107, p = .047). Monitoring salivary biomarkers provides information on mucosal immunity with impact in URS occurrence. Coaches could manipulate training loads to attenuate the physical stressors imposed on athletes, especially at demanding and stressful periods.

Short-term Resistance Training Increases APPL1 Content in the Liver and the Insulin Sensitivity of Mice Fed a Long-term High-fat Diet.

BACKGROUND: APPL1, an adapter protein, interact directly with adiponectin receptors mediating adiponectin signaling and acting as a critical regulator of the crosstalk between adiponectin and insulin signaling pathway. The inadequate level of physical activity, high-calorie intake, or both lead to adverse consequences on health, like insulin resistance. On the order hand, physical exercise acts positively in the insulin action. PURPOSE: Here, we investigated the effects of short-term resistance training (RT) on APPL1 content and adiponectin pathway in the liver of mice fed a long-term high-fat diet. METHODS: Swiss mice were distributed into 3 groups: Mice that fed a chow diet (CTR); Mice fed a high-fat diet for 16 months (HFD); and mice fed a high-fat diet for 16 months and submitted to a climbing ladder exercise (RT) for 7 days (HFD-EXE). RESULTS: The results show that short-term RT increases the APPL1 content but wasn't able to alter AdipoR1 and AdipoR2 content in the liver of HFD-EXE mice. However, this increase in the APPL1 content in response to RT was accompanied by improvement in the insulin sensitivity. CONCLUSION: In summary, our data suggested that short-term RT improves glycemic homeostasis and increases APPL1 in the hepatic tissue of mice treated with long-term high-fat diet.

Exploring the potential of salivary and blood immune biomarkers to elucidate physical frailty in institutionalized older women.

Identification of older populations at increased risk of physical frailty using biochemical approaches could improve screening accuracy. The aim of this study was to study the relationship between immune markers and independent components of physical frailty in institutionalized older women. A sample of 358 institutionalized-dwelling women, aged 75 years and older, were assessed for biosocial factors and general health status, pro and anti-inflammatory cytokines, sex steroid hormones, salivary anti-microbial proteins, blood cells counts and the five Fried's physical frailty components that allowed for classification of the sample into frail, prefrailty and not-frail subgroups. Results showed that cytokines IL-6, IL-10, IL-1ß, TNF-α, and the TNF-α/IL-10 ratio, mean corpuscular haemoglobin, salivary cortisol and α-amylase were all associated with frailty. Weakness and Exhaustion were the frailty components that were most strongly associated with these biomarkers. Salivary α-amylase was the biomarker that best explained frailty, as it was associated with all five components of physical frailty, and could be used as a potential screening tool. Future research needs to investigate the causal-effect association between salivary innate immune makers, susceptibility to infection and frailty.

Rho-kinase activity is upregulated in the skeletal muscle of aged exercised rats.

There is a gap in the knowledge regarding the regulation of glucose uptake in skeletal muscle during the development of insulin resistance in the elderly. Rho-Kinase (Rock) signaling has been demonstrated as a crucial mechanism related to glucose metabolism and insulin sensitivity in skeletal muscle. This kinase is involved in the insulin receptor substrate 1 (IRS1) phosphorylation, leading to glucose uptake stimulation in the skeletal muscle; however, the mechanisms elucidating the role of Rock regulation in the context of advanced ages are still limited. In this study, we submitted old Fischer 344 rats to short-term treadmill physical exercise protocol (5 days) and evaluated the glucose tolerance and proteins involved with Rock/insulin signaling in the skeletal muscle. Compared to young rats, the old rats showed glucose intolerance, hyperinsulinemia, and decreased phosphorylation in the proteins related to the insulin signaling pathway in the skeletal muscle, without changes in body mass and adiposity. Otherwise, when these rats were submitted to physical exercise, it was found decreased fasting glucose, higher glucose tolerance, decreased insulinemia, and upregulation of Rock2/pIRS1/pAkt/pGSK3ß/GLUT4 pathway in the skeletal muscle. In summary, the aging process did not change Rock signaling, but the physical exercise was able to increase Rock2 content and insulin signaling pathway in the skeletal muscle. This finding suggests the benefic role of physical exercise to advanced ages, promoting insulin-sensitive effects with Rho-kinase contribution.

Lifelong exercise practice and immunosenescence: Master athletes cytokine response to acute exercise.

The study aimed to analyze the effects of aging and lifelong training on the main pro- and anti-inflammatory cytokines, and the impact of acute exercise on the expression of these cytokines. Thirty-nine participants were allocated into 3 groups: young (31.8 ±â€¯3.00 yrs.), middle-aged (54.2 ±â€¯5.9 yrs.) and master athletes (53.1 ±â€¯8.8 yrs.) and performed a maximal incremental test on a cycle ergometer. Blood samples were obtained before (Pre), 10 min post-exercise (Post) and 1 h post-exercise (Post 1 h). Mean VO2max was similar for master athletes and youngers and higher compared to the middle-aged group. Resting values of the IL-1ra, IL-1ß, IL-4, and IL-8 were higher in master athletes compared to the young and middle-aged groups (P < 0.01), while the highest values of IL-10 and IL-17 were observed for the youngers (29.49 ±â€¯18.00 pg/mL and 66.24 ±â€¯23.23 pg/mL, respectively) with the middle-aged group showing the lowest values (2.13 ±â€¯1.40 pg/mL). Acute exercise effects (Post) were observed for IL-1ß in the master athletes group, IL-6 in the young group and IL-4 for both groups (P < 0.05). No Post effects were observed for the middle-age group for all cytokines. The TNF-α/IL-10 ratio was higher in all moments for the middle-aged (P < 0.05). In conclusion, lifelong training helps to maintain the balance of pro- and anti-inflammatory cytokines, together with IL-10 levels close to those found in young adults.