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.

Combined Training Improves Gene Expression Related to Immunosenescence in Obese Type 2 Diabetic Individuals.

Purpose: The aim of this study was to investigate the effects of moderate combined training (CT) on both the gene expression of pro- and anti-inflammatory markers and senescence in the immune system in peripheral blood mononuclear cells (PBMCs) and subcutaneous adipose tissue (SAT) of obese middle-aged individuals with type 2 diabetes (T2D). Methods: Thirty obese individuals (50.2 ± 9.4 years; body mass index: 31.8 ± 2.3 kg/m²) with T2D underwent 16 weeks of a CT group [CT; aerobic (50-60% of VO2max) plus resistance (50-75% of 1RM) training; 3 times/week, 70 min/session; n = 16)] or a control group (CG, n = 14). Nutritional patterns, muscle strength (1RM), cardiorespiratory fitness (VO2max), waist circumference (WC), body composition (Air Displacement Plethysmograph) and blood collections for biochemical (serum leptin, IL-2, IL-4, IL-6, IL-10, TNF-α and anti-CMV) and molecular (gene expression of leptin, IL-2, IL-4, IL-6, IL-10, TNF-α, PD-1, P16ink4a, CCR7, CD28 and CD27 in PBMCs and SAT) analyses were assessed before (Pre) and after (Post) the 16 weeks of the experimental period. Results: Significant decreases were observed in WC and IL4, TNF-α, PD-1 and CD27 expression in PBMCs for CT. Furthermore, significant increases were observed in 1RM and VO2max for CT after the experimental period. Conclusion: Moderate CT contributed to a reduction in the gene expression of markers associated to chronic inflammation and immunosenescence in PBMCs of obese middle-aged individuals with T2D.

Hemodynamic Predictors of Blood Pressure Responsiveness to Continuous Aerobic Training in Postmenopausal Hypertensive Women.

Blood pressure (BP) responses to recommended aerobic training can vary widely between individuals. Although studies demonstrate the role of exercise training in regulating BP responsiveness, predictive models are still unknown. This study aimed to identify hemodynamic predictive markers for the diagnosis of BP responsiveness based on baseline characteristics and postexercise ambulatory blood pressure (ABP) before an aerobic training program in postmenopausal women. Sixty-five postmenopausal women with essential hypertension were randomly allocated into the continuous aerobic training (CAT, n = 51) and nonexercising control (CON, n = 14) groups. CAT group cycled at moderate intensity three times a week for 12 weeks. Individuals who failed to decrease systolic blood pressure (SBP) were classified as nonresponders (NRs; n = 34) based on typical error of measurement. Baseline anthropometric, metabolic, cardiovascular, hemodynamic variables, and postexercise ABP was measured to predict BP responsiveness. A logistic regression model based on Baseline SBP [odds ratio (OR) = 1.202; 95% confidence interval (CI) = 1.080-1.338], SBP Nighttime (OR = 0.889; 95% CI = 0.811-0.975), and heart rate (HR) Nighttime (OR = 1.127; 95% CI = 1.014-1.254) were able to diagnose responders and NR individuals to BP reduction in response to CAT with 92.6% accuracy (P < 0.001; Sensitivity = 94.1%; Specificity = 79.4%). The findings highlight the potential value of baseline clinical characteristics as Baseline SBP, SBP, and HR Nighttime as markers for diagnosing BP responsiveness to recommended CAT in hypertension postmenopausal women. Clinical Trial Registration number: RBR-3xnqxs8.

Effect of Resistance Exercise Order on Cardiovascular Disease Risk Factors in Older Women: A Randomized Controlled Trial.

We compared the effects of two specific resistance training (RT) exercise orders on cardiovascular risk factors. Forty-four untrained older women (>60 years) were randomly assigned to three groups: control (CON, n = 15), multi-joint to single-joint (MJ-SJ, n = 14), and single-joint to multi-joint (SJ-MJ, n = 15) exercise orders. Training groups performed a whole-body RT program (eight exercises, 3 × 10−15 repetitions for each exercise) over 12 weeks in 3 days/week. Body fat, triglycerides, total cholesterol, HDL-c, LDL-c, VLDL-c, glucose, IL-6, IL-10, TNF-α, C-reactive protein, total radical-trapping antioxidant (TRAP), advanced oxidation protein products (AOPP), ferrous oxidation-xylenol (FOX), and nitric oxide concentrations (NOx) were determined pre- and post-intervention. Significant interaction group × time (p < 0.05) revealed reducing fat mass and trunk fat and improvements in glucose, LDL-c, IL-10, TNF-α, C-reactive protein, FOX, and AOPP concentrations in both training groups, without differences between them (p > 0.05). The results suggest that 12 weeks of RT, regardless of exercise order, elicit positive adaptations on body fat and metabolic biomarkers similarly in older women.

Metabolomic Response throughout 16 Weeks of Combined Aerobic and Resistance Exercise Training in Older Women with Metabolic Syndrome.

Increases in longevity and obesity have led to a higher prevalence of Metabolic Syndrome (MetS) and several chronic conditions, such as hypertension. The prevalence of MetS and hypertension increases with advancing age and their detrimental effects on health can be attenuated by physical activity. Combined aerobic and resistance exercise training (CT) is recommended to maintain good health in older adults and is known to generate important metabolic adaptations. In this study we performed a metabolomics analysis, based on Hydrogen Nuclear Magnetic Resonance (1H NMR), to investigate the kinetics of changes in metabolism in non-physically active older women with MetS in response to 16 weeks of CT. A subset of women with MetS were selected from a larger randomized trial (that included men and women without MetS), with 12 participants on CT and 13 from the Control Group (CG). CT comprised walking/running at 63% of VO2max, three times/week, and resistance training (RT), consisting of 15 repetitions of seven exercises at moderate intensity, twice/week. Serum metabolomic profile was analysed at baseline (0W), 4 (4W), 8 (8W), 12 (12W) and 16 weeks (16W) for CT or CG. Cardiorespiratory fitness, RT load, blood pressure, body composition, lipid and glycaemic profile were also assessed. After 16 weeks CT increased cardiorespiratory fitness (13.1%, p < 0.05) and RT load (from 48% in the lat pulldown to 160% in the leg press, p < 0.05), but there were no changes in MetS parameters, such as body composition (Body Mass, Body Mass Index (BMI), body fat percentage and waist circumference), blood pressure, lipid and glycaemic profile. However, we identified potential higher substrate to the tricarboxylic acid cycle (increase in 2-Oxobutyrate from 0W (0.0029 ± 0.0009) to 4W (0.0038 ± 0.0011) and 8W (0.0041 ± 0.0015), p < 0.05), followed by alterations (different from 0W, p < 0.05) in the production of ketone bodies (3-Hydroxybutyrate, 0W (0.0717 ± 0.0377) to 16W (0.0397 ± 0.0331), and Acetoacetate, 0W (0.0441 ± 0.0240) to 16W (0.0239 ± 0.0141)), which together might explain the known improvement in fatty acid oxidation with exercise. There was also a late increase in ornithine at 16W of CT. Further studies are needed to investigate the association between these metabolic pathways and clinical outcomes in this population.

Comprehensive Time-Course Effects of Combined Training on Hypertensive Older Adults: A Randomized Control Trial.

The aim was to identify whether 16 weeks of combined training (Training) reduces blood pressure of hypertensive older adults and what the key fitness, hemodynamic, autonomic, inflammatory, oxidative, glucose and/or lipid mediators of this intervention would be. Fifty-two individuals were randomized to either 16 weeks of Training or control group who remained physically inactive (Control). Training included walking/running at 63% of V˙O2max, three times per week, and strength training, consisting of one set of fifteen repetitions (seven exercises) at moderate intensity, twice per week. Both groups underwent a comprehensive health assessment at baseline (W0) and every four weeks, for 16 weeks total. p-value ≤ 0.05 was set as significant. Training did not reduce blood pressure. It increased V˙O2max after eight weeks and again after 16 weeks (~18%), differently from the Control group. At 16 weeks, Training increased strength (~8%), slightly reduced body mass (~1%), and reduced the number of individuals with metabolic syndrome (~7%). No other changes were observed (heart rate, carotid compliance, body composition, glycemic and lipid profile, inflammatory markers and oxidative profile, vasoactive substances, heart rate variability indices). Although Training increased cardiorespiratory fitness and strength, Training was able to reduce neither blood pressure nor a wide range of mediators in hypertensive older adults, suggesting other exercise interventions might be necessary to improve overall health in this population. The novelty of this study was the time-course characterization of Training effects, surprisingly demonstrating stability among a comprehensive number of health outcomes in hypertensive older adults, including blood pressure.

Impacts of high-intensity exercise on the metabolomics profile of human skeletal muscle tissue.

The study aimed to identify and quantify the metabolites profile and metabolic pathways in human muscle tissue engaged during exhaustive high-intensity cycling exercise. Seven healthy physically active men performed a graded exercise test and an exhaustive supramaximal effort at 115% of maximal aerobic power with muscles biopsies performed in rest and immediately after exhaustion for quantifying of muscle metabolites changes by 1 H-NMR spectroscopy. The time until exhaustion (tlim) recorded was 224.7 ± 35.5 s whereas the muscle pH at exhaustion was 6.48 ± 0.05. A total of 54 metabolites were identified and quantified. The most enriched and impacted pathways included: beta oxidation of very long chain fatty acids, mitochondrial electron transport chain, alanine aspartate, and glutamate metabolism, citric acid cycle, arginine biosynthesis, propanoate metabolism, threonine and 2-oxobutanoate degradation and pyruvate metabolism. In addition, the muscle concentrations in Post exercise, compared to Pre increased significantly (p < 0.0398) for fumarate (42.0%), succinate (101.2%), glucose (249.7%), lactate (122.8%), O-acetylcarnitine (164.7%), glycerol (79.3%), AMP (288.2%), 2-oxobutyrate (121.0%), and methanol (58.5%), whereas decreased significantly (p < 0.010) for creatine phosphate (-70.2%), ADP (-56.5%), carnitine (-33.5%), and glutamate (-42.3%). Only the succinate was significantly correlated with tlim (r = -0.76; p = 0.0497). Besides the classical expected contribution of glycolytic and phosphagen energetic pathways, it was demonstrated that the high-intensity exercise is also associated with pathways indicatives of amino acid and fatty acid oxidation metabolisms, highlighting the inverse relation between changes in the intramuscular succinate levels and tlim.

Serum metabolites associated with increased insulin resistance and low cardiorespiratory fitness in overweight adolescents.

BACKGROUND AND AIMS: Obesity affects metabolism, increasing the risk of developing non-communicable diseases in adolescence, due to excess adipose tissue and low cardiorespiratory fitness (CRF). The metabolomics approach allows the elucidation of metabolites, which may have the concentrations altered by several factors, such as body composition (BC). We aimed to analyze the metabolomic profile of normal-weight and overweight adolescents and associate the metabolites with clinical markers related to BC, insulin resistance (IR), and CRF. METHODS AND RESULTS: The sample was composed of 57 adolescents and divided into two groups: the normal-weight group (NWG, n = 24) and the overweight group (OWG, n = 33). They underwent blood collection and anthropometric, BC, and CRF assessment. Blood serum samples were analyzed by 1H-NMR spectroscopy (600 MHz). The OWG presented higher values of body weight (BW), body mass index (BMI), waist circumference (WC), fasting glucose, insulin, IR, cholesterol, and percentage of fat mass (%FM) and lower levels of peak oxygen consumption (VO2 peak) compared with the NWG. The OWG presented lower concentrations of 3-hydroxyisovalerate, glutamate, and methionine as well as higher concentrations of aspartate, asparagine, creatine, glycerol, myo-inositol, proline, pyruvate, tyrosine, and valerate compared with the NWG. The concentrations of glutamate, myo-inositol, creatine, methionine, and valerate correlated with %FM; pyruvate and valerate positively correlated with IR; and glutamate, tyrosine, and valerate negatively correlated with CRF. CONCLUSION: Changes in the BC lead to changes in the metabolomic profile of adolescents, and the altered metabolites are associated with increased IR and low CRF. These results indicate new targets for health monitoring and prevention of cardiovascular and metabolic diseases in adolescents.

Association Between Changes in Serum and Skeletal Muscle Metabolomics Profile With Maximum Power Output Gains in Response to Different Aerobic Training Programs: The Times Study.

Purpose: High heterogeneity of the response of cardiorespiratory fitness (CRF) to standardized exercise doses has been reported in different training programs, but the associated mechanisms are not widely known. This study investigated whether changes in the metabolic profile and pathways in blood serum and the skeletal muscle are associated with the inter-individual variability of CRF responses to 8-wk of continuous endurance training (ET) or high-intensity interval training (HIIT). Methods: Eighty men, young and sedentary, were randomized into three groups, of which 70 completed 8 wk of intervention (> 90% of sessions): ET, HIIT, or control. Blood and vastus lateralis muscle tissue samples, as well as the measurement of CRF [maximal power output (MPO)] were obtained before and after the intervention. Blood serum and skeletal muscle samples were analyzed by 600 MHz 1H-NMR spectroscopy (metabolomics). Associations between the pretraining to post-training changes in the metabolic profile and MPO gains were explored via three analytical approaches: (1) correlation between pretraining to post-training changes in metabolites' concentration levels and MPO gains; (2) significant differences between low and high MPO responders; and (3) metabolite contribution to significantly altered pathways related to MPO gains. After, metabolites within these three levels of evidence were analyzed by multiple stepwise linear regression. The significance level was set at 1%. Results: The metabolomics profile panel yielded 43 serum and 70 muscle metabolites. From the metabolites within the three levels of evidence (15 serum and 4 muscle metabolites for ET; 5 serum and 1 muscle metabolites for HIIT), the variance in MPO gains was explained: 77.4% by the intervention effects, 6.9, 2.3, 3.2, and 2.2% by changes in skeletal muscle pyruvate and valine, serum glutamine and creatine phosphate, respectively, in ET; and 80.9% by the intervention effects; 7.2, 2.2, and 1.2% by changes in skeletal muscle glycolate, serum creatine and creatine phosphate, respectively, in HIIT. The most changed and impacted pathways by these metabolites were: arginine and proline metabolism, glycine, serine and threonine metabolism, and glyoxylate and dicarboxylate metabolism for both ET and HIIT programs; and additional alanine, aspartate and glutamate metabolism, arginine biosynthesis, glycolysis/gluconeogenesis, and pyruvate metabolism for ET. Conclusion: These results suggest that regulating the metabolism of amino acids and carbohydrates may be a potential mechanism for understanding the inter-individual variability of CRF in responses to ET and HIIT programs.

Higher Physical Activity Level Improves Leptin Concentrations in Spinal Cord Injury Subjects.

The present study was designed to compare the body composition and indicators of chronic inflammatory grade, such as leptin, adiponectin, and resistin concentrations in irregularly active and active SCI subjects. Thirty-two male subjects participated in this study. They were divided into three groups: able-bodied control irregularly active (control, n = 11), irregularly active with SCI (SCI-IA, n = 8), and physically active with SCI (SCI-PA, n = 13). The enzyme-linked immunosorbent assay (ELISA) assessed serum concentrations of leptin, adiponectin, and resistin. All volunteers performed the maximum oxygen uptake (VO2max) test, 24 h total energy expenditure (TEE), and body composition by skinfold thicknesses. Leptin concentrations were higher in the SCI-IA group when compared to the other groups, while no significant differences were found between the SCI-PA and control cohorts. In addition, no significant differences were found among groups for serum adiponectin and resistin concentrations either. The SCI-PA group showed significantly higher values for TEE and VO2max when compared to the other groups. Percentages of body fat and circumference were decreased in the control and SCI-PA groups when compared to the SCI-IA cohort. Associations between leptin and cardiorespiratory capacity and anthropometric markers were also observed. Our findings highlight that the lack of physical activity in the SCI subjects leads to poor general physical fitness and higher levels of body adiposity, which may induce hyperleptinemia, an essential marker for cardiometabolic disorders.

Understanding the Relationship between Intrinsic Cardiorespiratory Fitness and Serum and Skeletal Muscle Metabolomics Profile.

Intrinsic cardiorespiratory fitness (iCRF) indicates the CRF level in the sedentary state. However, even among sedentary individuals, a wide interindividual variability is observed in the iCRF levels, whose associated molecular characteristics are little understood. This study aimed to investigate whether serum and skeletal muscle metabolomics profiles are associated with iCRF, measured by maximal power output (MPO). Seventy sedentary young adults were submitted to venous blood sampling, a biopsy of the vastus lateralis muscle and iCRF assessment. Blood serum and muscle tissue samples were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy. Metabolites related to iCRF were those supported by three levels of evidence: (1) correlation with iCRF, (2) significant difference between individuals with low and high iCRF, and (3) metabolite contribution to significant pathways associated with iCRF. From 43 serum and 70 skeletal muscle analyzed metabolites, iCRF was positively associated with levels of betaine, threonine, proline, ornithine, and glutamine in serum and lactate, fumarate, NADP+, and formate in skeletal muscle. Serum betaine and ornithine and skeletal muscle lactate metabolites explained 31.2 and 16.8%, respectively, of the iCRF variability in addition to body mass. The results suggest that iCRF in young adults is positively associated with serum and skeletal muscle metabolic levels, indicative of the amino acid and carbohydrate metabolism.

Obesity Increases Gene Expression of Markers Associated With Immunosenescence in Obese Middle-Aged Individuals.

Recently, it has been argued that obesity leads to a chronic pro-inflammatory state that can accelerate immunosenescence, predisposing to the early acquisition of an immune risk profile and health problems related to immunity in adulthood. In this sense, the present study aimed to verify, in circulating leukocytes, the gene expression of markers related to early immunosenescence associated with obesity and its possible relationships with the physical fitness in obese adults with type 2 diabetes or without associated comorbidities. The sample consisted of middle-aged obese individuals (body mass index (BMI) between 30-35 kg/m²) with type 2 diabetes mellitus (OBD; n = 17) or without associated comorbidity (OB; n = 18), and a control group of eutrophic healthy individuals (BMI: 20 - 25 kg/m²) of same ages (E; n = 18). All groups (OBD, OB and E) performed the functional analyses [muscle strength (1RM) and cardiorespiratory fitness (VO2max)], anthropometry, body composition (Air Displacement Plethysmograph), blood collections for biochemical (anti-CMV) and molecular (gene expression of leptin, IL-2, IL-4, IL-6, IL-10, TNF-α, PD-1, P16ink4a, CCR7, CD28 and CD27) analyses of markers related to immunosenescence. Increased gene expression of leptin, IL-2, IL-4, IL-10, TNF-α, PD-1, P16ink4a, CCR7 and CD27 was found for the OBD and OB groups compared to the E group. Moreover, VO2max for the OBD and OB groups was significantly lower compared to E. In conclusion, obesity, regardless of associated disease, induces increased gene expression of markers associated with inflammation and immunosenescence in circulating leukocytes in obese middle-aged individuals compared to a eutrophic group of the same age. Additionally, increased adipose tissue and markers of chronic inflammation and immunosenescence were associated to impairments in the cardiorespiratory capacity of obese middle-aged individuals.

Influence of Resistance Training Exercise Order on Muscle Strength, Hypertrophy, and Anabolic Hormones in Older Women: A Randomized Controlled Trial.

Tomeleri, CM, Ribeiro, AS, Nunes, JP, Schoenfeld, BJ, Souza, MF, Schiavoni, D, Junior, PS, Cavaglieri, CR, Cunha, PM, Venturini, D, Barbosa, DS, and Cyrino, ES. Influence of resistance training exercise order on muscle strength, hypertrophy, and anabolic hormones in older women: a randomized controlled trial. J Strength Cond Res 34(11): 3103-3109, 2020-The purpose of this study was to analyze the effects of resistance training (RT) exercise order on muscle strength, hypertrophy, and anabolic hormones in older women. Forty-four older women were randomly assigned to 1 of 3 groups: a nonexercise control group (CON, n = 15) and two RT groups that performed a 12-week RT program in a multijoint to single-joint order (MJ-SJ, n = 14), or in a single-joint to multijoint order (SJ-MJ, n = 15). The RT protocol (3×/week) encompassed 8 exercises, with 3 sets of 10-15 repetitions performed per exercise. One repetition maximum tests were used to evaluate muscle strength; dual-energy X-ray absorptiometry was used to estimate lean soft tissue. Both training groups showed significant and similar increases in muscle strength (MJ-SJ = 16.4%; SJ-MJ = 12.7%) and mass (MJ-SJ = 7.5%; SJ-MJ = 6.1%), whereas there were no significant changes in testosterone and insulin-like growth factor 1. The results suggest that both approaches are similarly effective in eliciting morphofunctional improvements in older women.

Altered metabolomic profiling of overweight and obese adolescents after combined training is associated with reduced insulin resistance.

Exercise training and a healthy diet are the main non-pharmacological strategies for treating chronic conditions, such as obesity and insulin resistance (IR), in adolescents. However, the isolated metabolic changes caused by exercise training without dietary intervention have not yet been established. We investigated how combined training (CT) without dietary intervention altered the concentrations of serum metabolites, biochemical, anthropometric and functional parameters in overweight and obese adolescents. Thirty-seven adolescents (14.6 ± 1.05 years), of both sexes, were randomly assigned to the control group (CG, n = 19) or the training group (TG, n = 18). The CT was composed by resistance training and aerobic training performed in the same session (~ 60 min), three times a week, for 12 weeks. All assessments were performed pre and post-intervention. Metabolomics analyses were conducted using nuclear magnetic resonance spectroscopy (1H NMR) in a 600 MHz spectrometer. There was a decrease in body weight (BW), body mass index (BMI), waist circumference (WC), % body fat (%BF), fasting glucose, insulin levels, and insulin resistance (IR), by HOMA-IR, in the TG. An increase in fat-free mass (FFM) was also observed in the CG. The metabolic changes were given mainly by changes in the levels of metabolites 2-oxoisocaproate (↓TG), 3-hydroxyisobutyrate (↑CG and ↓TG), glucose (↓TG), glutamine (↓CG and ↑TG) and pyruvate (↓TG). These findings demonstrate the positive effects of CT program without dietary intervention on metabolomic profile, body composition, biochemical markers, and glucose metabolism in overweight and obese adolescents.

Acute low- compared to high-load resistance training to failure results in greater energy expenditure during exercise in healthy young men.

The objective of the present study was to verify the energy expenditure (EE), energy system contributions and autonomic control during and after an acute low-load or high-load resistance training (RT) protocol to momentary failure (MF) in young adults. Eleven young men (22 ± 3 yrs, 71.8 ± 7.7 kg; 1.75 ± 0.06 m) underwent a randomized crossover design of three knee extension acute protocols: a low-load RT [30% of their maximal strength (1RM); RT30] or a high-load RT (80% of 1RM; RT80) protocol, with all sets being performed to MF; or a control session (Control) without exercise. Participants were measured for EE, energy system contributions, and cardiac autonomic control before, during, and after each exercise session. Exercise EE was significantly higher for RT30 as compared to RT80. Furthermore, post measurements of blood lactate levels and the anaerobic lactic system contribution were significantly greater for RT30 as compared to RT80. In addition, parasympathetic restoration was lower for RT30 as compared to RT80. In conclusion, a low-load (30% 1RM) RT session produced higher EE during exercise than a high-load (80% 1RM) RT session to MF, and may be a good option for fitness professionals, exercise physiologists, and practitioners when choosing the optimal RT protocol that provides more EE, especially for those who want or need to lose weight.

Time-Course of Changes in Physiological, Psychological, and Performance Markers following a Functional-Fitness Competition.

Functional Fitness Training (FFT) programs are characterized by utilizing a high volume of training and using a variety of high intensity exercises. While FFT are growing in the number of practitioners and popularity, the relationship between physiological biomarkers and subjective scales in the specific context of FFT has not yet been evaluated in the literature. The purpose of the present study was to monitor the time-course response of cytokines (IL-10 and 1L-1ß), immune variables (C-reactive protein -CRP and immunoglobulin A-IgA), hormonal milieu (cortisol-C, total testosterone-TT, free testosterone-FT and testosterone/cortisol-T/C ratio), creatine kinase-CK, muscle performance (countermovement jump height) and perceived well-being (WB) following a functional fitness competition. Nine amateur male athletes (age 27.1 ± 4.1 years; training experience 2.2 ± 1.3 years) completed five workouts over three consecutive days of FFT-competition. All variables were measured before, 24 h, 48 h, and 72 h following the last day of competition. The FFT-competition induced a decrease in IL10/IL1ß ratio approximately 5% after 24h, 21% after 48h and 31% after 72h. Delta T/C ratio remained unchanged during the post-competition period. IgA displayed a significant increase 24h and 72h post FFT-competition. The WB status score was higher 72h after the FFT-competition as compared with pre-competition. The present findings suggest that FFT-competition induces transient changes in some inflammatory and hormonal biomarkers, and perceived well-being seems to be efficient to detect changes in muscle performance.

Augmented Anabolic Responses after 8-wk Cycling with Blood Flow Restriction.

INTRODUCTION: Low-intensity endurance training (ET) performed with blood flow restriction (BFR) can improve muscle strength, cross-sectional area (CSA) and cardiorespiratory capacity. Whether muscle strength and CSA as well as cardiorespiratory capacity (i.e., V˙O2max) and underlying molecular processes regulating such respective muscle adaptations are comparable to resistance and ET is unknown. PURPOSE: To determine the respective chronic (i.e., 8 wk) functional, morphological, and molecular responses of ET-BFR training compared with conventional, unrestricted resistance training (RT) and ET. METHODS: Thirty healthy young men were randomly assigned to one of three experimental groups: ET-BFR (n = 10, 4 d·wk, 30-min cycling at 40% of V˙O2max), RT (n = 10, 4 d·wk, 4 sets of 10 repetitions leg press at 70% of one repetition maximum with 60 s rest) or ET (n = 10, 4 d·wk, 30-min cycling at 70% of V˙O2max) for 8 wk. Measures of quadriceps CSA, leg press one repetition maximum, and V˙O2max as well as muscle biopsies were obtained before and after intervention. RESULTS: Both RT and ET-BFR increased muscle strength and hypertrophy responses. ET-BFR also increased V˙O2max, total cytochrome c oxidase subunit 4 isoform 1 abundance and vascular endothelial growth factor mRNA abundance despite the lower work load compared to ET. CONCLUSIONS: Eight weeks of ET-BFR can increase muscle strength and induce similar muscle hypertrophy responses to RT while V˙O2max responses also increased postintervention even with a significantly lower work load compared with ET. Our findings provide new insight to some of the molecular mechanisms mediating adaptation responses with ET-BFR and the potential for this training protocol to improve muscle and cardiorespiratory capacity.

Abnormal brown adipose tissue mitochondrial structure and function in IL10 deficiency.

BACKGROUND: Inflammation is the most relevant mechanism linking obesity with insulin-resistance and metabolic disease. It impacts the structure and function of tissues and organs involved in metabolism, such as the liver, pancreatic islets and the hypothalamus. Brown adipose tissue has emerged as an important component of whole body energy homeostasis, controlling caloric expenditure through the regulation of non-shivering thermogenesis. However, little is known about the impact of systemic inflammation on the structure and function of brown adipose tissue. METHODS: The relations between IL10 and mitochondria structure/function and also with thermogenesis were evaluated by bioinformatics using human and rodent data. Real-time PCR, immunoblot, fluorescence and transmission electron microscopy were employed to determine the effect of IL10 in the brown adipose tissue of wild type and IL10 knockout mice. FINDINGS: IL10 knockout mice, a model of systemic inflammation, present severe structural abnormalities of brown adipose tissue mitochondria, which are round-shaped with loss of cristae structure and increased fragmentation. IL10 deficiency leads to newborn cold intolerance and impaired UCP1-dependent brown adipose tissue mitochondrial respiration. The reduction of systemic inflammation with an anti-TNFα monoclonal antibody partially rescued the structural but not the functional abnormalities of brown adipose tissue mitochondria. Using bioinformatics analyses we show that in both humans and mice, IL10 transcripts correlate with mitochondrial lipid metabolism and caspase gene expression. INTERPRETATION: IL10 and systemic inflammation play a central role in the regulation of brown adipose tissue by controlling mitochondrial structure and function. FUND: Sao Paulo Research Foundation grant 2013/07607-8.

Low-intensity resistance training with partial blood flow restriction and high-intensity resistance training induce similar changes in skeletal muscle transcriptome in elderly humans.

We aimed to investigate the mechanisms underlying muscle growth after 12 weeks of resistance training performed with blood flow restriction (RT-BFR) and high-intensity resistance training (HRT) in older individuals. Participants were allocated into the following groups: HRT, RT-BFR, or a control group. High-throughput transcriptome sequencing was performed by the Illumina HiSeq 2500 platform. HRT and RT-BFR presented similar increases in the quadriceps femoris cross-sectional area, and few genes were differently expressed between interventions. The small differences in gene expression between interventions suggest that similar mechanisms may underpin training-induced muscle growth.

Anaerobic metabolism induces greater total energy expenditure during exercise with blood flow restriction.

PURPOSE: We investigated the energy system contributions and total energy expenditure during low intensity endurance exercise associated with blood flow restriction (LIE-BFR) and without blood flow restriction (LIE). METHODS: Twelve males participated in a contra-balanced, cross-over design in which subjects completed a bout of low-intensity endurance exercise (30min cycling at 40% of [Formula: see text]) with or without BFR, separated by at least 72 hours of recovery. Blood lactate accumulation and oxygen uptake during and after exercise were used to estimate the anaerobic lactic metabolism, aerobic metabolism, and anaerobic alactic metabolism contributions, respectively. RESULTS: There were significant increases in the anaerobic lactic metabolism (P = 0.008), aerobic metabolism (P = 0.020), and total energy expenditure (P = 0.008) in the LIE-BFR. No significant differences between conditions for the anaerobic alactic metabolism were found (P = 0.582). Plasma lactate concentration was significantly higher in the LIE-BFR at 15min and peak post-exercise (all P≤0.008). Heart rate was significantly higher in the LIE-BFR at 10, 15, 20, 25, and 30min during exercise, and 5, 10, and 15min after exercise (all P≤0.03). Ventilation was significantly higher in the LIE-BFR at 10, 15, and 20min during exercise (all P≤0.003). CONCLUSION: Low-intensity endurance exercise performed with blood flow restriction increases the anaerobic lactic and aerobic metabolisms, total energy expenditure, and cardiorespiratory responses.