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.

Effects of lifelong training on senescence and mobilization of T lymphocytes in response to acute exercise.

BACKGROUND/PURPOSE: Ageing has profound impact on the immune system, mainly on T-cells. However, it has been suggested that chronic exercise may delay immunosenescence. Master athletes represent an interesting sub-demographic group to test this theory since they maintain a high training frequency and load throughout life. The purpose of this study was to evaluate the effects of lifelong training on the senescence and mobilization of T lymphocytes in response to acute exercise. MATERIAL AND METHODS: Nineteen athletes who regularly participated in training and competitions for more than 20 years throughout their lives and a control group of 10 healthy individuals participated in this study. All subjects performed a progressive test to exhaustion on a cycle ergometer. Blood samples were obtained before (Pre), 10 min after the test (Post) and 1 h after the test (1h). Phenotypic study of peripheral blood T-cells was performed by flow cytometry. Genes of interest expression was done on T-cells purified by cell sorting. RESULTS: Master athletes had a lower percentage of senescent naïve, central memory and effector memory CD8+ T-cells and senescent naïve and effector memory CD4+ T-cells. Age had a positive effect on SLEC CD8+ T-cells and a negative effect on naïve CD8+ T-cells. VO2max positively correlated with the proportion of naïve CD4+ T-cells and negatively correlated with the percentage of total lymphocytes. No differences were founded for CD4+ and CD8+ T-cells and their subsets between master athletes and the control group at all times of measurement. No differences were observed in the CD45RA expressing effector memory cells (EMRA) for the various study conditions. The mRNA expression of the CCR7 gene for naïve CD8+ T-cells and the Fas-L gene for effector-terminal CD8+ T-cells was not different between masters and controls and did not change in response to the maximal protocol test. CONCLUSION: In conclusion, maintaining high levels of aerobic fitness during the natural course of aging may help prevent the accumulation of senescent T-cells.

Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletes.

PURPOSE: The purpose of this study was to quantify and characterize peripheral blood regulatory T cells (Tregs), as well as the IL-10 plasma concentration, in Masters athletes at rest and after an acute exhaustive exercise test. METHODS: Eighteen Masters athletes (self-reported training: 24.6 ± 1.83 years; 10.27 ± 0.24 months and 5.45 ± 0.42 h/week per each month trained) and an age-matched control group of ten subjects (that never took part in regular physical training) volunteered for this study. All subjects performed an incremental test to exhaustion on a cycle ergometer. Blood samples were obtained before (Pre), 10 min into recovery (Post), and 1 h after the test (1 h). RESULTS: Absolute numbers of Tregs were similar in both groups at rest. Acute exercise induced a significant increase in absolute numbers of Tregs at Post (0.049 ± 0.021 to 0.056 ± 0.024 × 109/L, P = 0.029 for Masters; 0.048 ± 0.017 to 0.058 ± 0.020 × 109/L, P = 0.037 for control) in both groups. Treg mRNA expression for FoxP3, IL-10, and TGF-ß in sorted Tregs was similar throughout the trials in both groups. Masters athletes showed a higher percentage of subjects expressing the FoxP3 (100% for Masters vs. 78% for Controls, P = 0.038) and TGF-ß (89% for Masters vs. 56% for Controls, P = 0.002) after exercise and a higher plasma IL-10 concentration (15.390 ± 7.032 for Masters vs. 2.411 ± 1.117 for control P = 0.001, ES = 2.57) at all timepoints. KLRG1 expression in Tregs was unchanged. CONCLUSION: Our findings showed that Masters athletes have elevated anti-inflammatory markers and maintain the number of Tregs, and may be an adaptive response to lifelong training.

Acute Hematological and Inflammatory Responses to High-intensity Exercise Tests: Impact of Duration and Mode of Exercise.

The purpose of this study was to investigate the hematological and inflammatory responses to 4 maximal high-intensity protocols, considering energy expenditure in each test. 9 healthy volunteers performed 4 high-intensity exercise tests of short [Wingate (WANT); Repeated-sprints (RSA)] and long durations [Continuous VO2 test (VCONT); intermittent VO2 test (VINT)] in a cycle-ergometer, until exhaustion. Hematological parameters and IL-6, IL-10 and creatine kinase (CK) levels were determined before (PRE), POST, 30 min, 1, 2, 12 and 24 h after the end of the protocols. Additionally, energy expenditure was determined. Leucocytes, erythrocytes and lymphocytes increased at POST and returned to PRE values at 30 min for all protocols. Lymphocytes had a second decreased at 2 h and granulocytes increased at 2 h when compared to PRE. Both variables returned to PRE values between 12-24 h into recovery. The magnitude of response for IL-6 was greater in VINT and for IL-10 in VCONT. There was no association of energy expenditure within each exercise protocol with the pattern of IL-6, IL-10 and CK responses to the exercise protocols. The present finding support that similar responses after continuous or intermittent acute protocols are observed when exercises are performed to volitional failure, regardless of the duration and mode of exercise.

Variation in plasma cytokine concentration during a training season in elite kayakers.

BACKGROUND: The purpose of this study was to investigate the differences in cytokines levels in the peripheral blood of kayakers at different moments of training. METHODS: The sample comprised 12 elite kayakers preparing for the Beijing Olympic Games. Blood samples were collected at different time points of the training season: baseline (t0-November) after 6 weeks of off-training and before the start of the training season; t1 (January) at week 11 after a period of high-volume training; t2 (April) at week 26 at the end of a period of high intensity training sessions; t3 (June) at week 31 after a competitive period. RESULTS: Decreases in cytokine levels were found for IL-1ß and IL-18 at t1. IL-1 then increased throughout the remaining training season while IL-18 leveled off towards the end of the season. IL-1ra showed an exponential increase at t2 before leveling-off in the last period of training. No significant changes were found for IL-6, IFN-γ and TNF-α. No differences were observed in the magnitude and pattern of cytokines changes across the training season between the elite female and male kayakers. CONCLUSIONS: Increases in training volume were able to induce decreases in pro-inflammatory plasma cytokine coinciding with the reported increase in upper respiratory tract infections in the kayakers.

Strength Training Decreases Inflammation and Increases Cognition and Physical Fitness in Older Women with Cognitive Impairment.

Introduction: Cognitive impairment that affects older adults is commonly associated with an inflammatory imbalance, resulting in decreased physical fitness. Exercise has been pointed to mitigate immunosenescence and cognitive impairment associated with aging, while increase in physical fitness. However, few studies explored the relationship between changes in cytokine concentration and improvement on cognition due to elastic band strength training. The aim of this study was to investigate the effects of strength training on pro-and anti-inflammatory cytokines, hematological markers and physical fitness of older women with cognitive impairment. Methods: Thirty-three women (82.7 ± 5.7 years old) participated in the study and were divided in two groups: strength exercise training group (ST; n = 16) and Control Group (CG; n = 17) and were evaluated before and after 28 weeks of the exercise program. The CG did not undergo any type of exercise programs. Data for IL-10, TNF-α, IFN-γ, C-Reactive Protein (CRP), white blood counts (WBC), red blood counts (RBC), Mini Mental State Examination (MMSE) and physical fitness tests were analyzed in both moments. Results: IL-10 increased in the ST group without changes in CG. TNF-α and CRP increased in the control group while no changes were observed for IFN-γ in both groups. Strength training decreased leukocyte and lymphocyte counts and increase hemoglobin, mean cell volume and mean cell hemoglobin concentration. The MMSE score increased in strength training group but remained unchanged in the control group. A correlation between the variation of granulocyte counts and the MMSE scores was also observed within the total sample. An improvement in physical fitness was observed with strength training. Conclusion: Resistance exercise promoted better anti-inflammatory balance and physical performance simultaneously with an increase in cognitive profile in older women with cognitive impairment.