Effects of combined training on nonshivering thermogenic activity of muscles in individuals with overweight and type 2 diabetes.

BACKGROUND: Increased thermogenic activity has shown to be a promising target for treating and preventing obesity and type 2 diabetes (T2DM). Little is known about the muscular influence on nonshivering thermogenesis (NST), and it remains unclear whether physical training and potential metabolic improvements could be associated with changes in this type of thermogenic activity. OBJECTIVE: The present study aimed to assess muscular NST activity in overweight and T2DM before and after a combined training period (strength training followed by aerobic exercise). METHODS: Nonshivering cold-induced 18-fluoroxyglucose positron emission computed tomography (18F-FDG PET/CT) was performed before and after 16 weeks of combined training in 12 individuals with overweight and T2DM. The standard uptake value (SUV) of 18F-FDG was evaluated in skeletal muscles, the heart and the aorta. RESULTS: Muscles in the neck region exhibit higher SUV pre- and posttraining. Furthermore, a decrease in glucose uptake by the muscles of the lower and upper extremities and in the aorta was observed after training when adjusted for brown adipose tissue (BAT). These pre-post effects are accompanied by increased cardiac SUV and occur concurrently with heightened energy expenditure and metabolic improvements. CONCLUSIONS: Muscles in the neck region have greater metabolic activity upon exposure to cold. In addition, combined training appears to induce greater NST, favoring the trunk and neck region compared to limbs based on joint work and adaptations between skeletal muscles and BAT.

Associations Between Fat and Lean Mass Indexes and Physical Performance in Prefrail and Frail Older Women.

Age-related changes in body composition have been associated with reduced physical performance. However, the relationship of fat and lean mass indexes with physical performance in the setting of frailty is yet to be clearly established. We investigated the association between fat and lean mass indexes and physical performance in prefrail and frail older women. Fifty-one community-dwelling women 65 years and older (mean age 76 years) were classified as prefrail or frail according to a modified frailty phenotype. Body composition was estimated by dual-energy X-ray absorptiometry, while physical performance was assessed via the following tests: Berg balance scale, timed-stands, timed up-and-go test, 6-minute walk test, and the short performance physical battery. Correlation coefficients were determined to assess the association between body composition and physical performance parameters. Associations between continuous variables with a p-value <0.05 were included in a linear regression analysis. All fat mass indexes predicted a reduced performance in at least one functional test. Among the lean mass indexes, only leg lean mass adjusted by body fat mass was directly associated with better physical performance. Our findings indicate that fat mass indexes may have a greater impact on physical performance than lean mass in frail and prefrail older women.

Hypotensive effects of exercise training: are postmenopausal women with hypertension non-responders or responders?

We tested the hypothesis that increasing the exercise dose or changing the exercise mode would augment hypotensive effects when traditional aerobic exercise training failed to produce it in postmenopausal women. Sixty-five postmenopausal women with essential hypertension were randomly allocated into the continuous aerobic training (CAT) and non-exercising control (CON) groups. CAT group cycled at moderate intensity 3 times a week for 12 weeks. Individuals who failed to decrease systolic blood pressure (BP) were classified as non-responders (n = 34) and performed an additional 12 weeks of exercise training with either increasing the exercise dose or changing the exercise mode. The 3 follow-up groups were continuous aerobic training 3 times a week, continuous aerobic training 4 times a week, and high-intensity interval training. After the first 12 weeks of exercise training, systolic BP decreased by 1.5 mmHg (NS) with a wide range of inter-individual responses (-23 to 23 mmHg). Sixty-seven percent of women who were initially classified as non-responders participated in the second training period. Sixty percent of women who participated in continuous exercise training 3 or 4 times a week at greater exercise intensities reduced systolic BP. All (100%) of the women who performed high-intensity interval training experienced significant reductions in systolic BP. Traditional aerobic exercise was not sufficient to decrease BP significantly in the majority of postmenopausal women. However, those women who were not sensitive to recommended exercise may reduce BP if they were exposed to continuous aerobic exercise at higher intensities and/or volumes or a different mode of exercise.

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.

Moderate-Intensity Combined Training Induces Lipidomic Changes in Individuals with Obesity and Type 2 Diabetes.

CONTEXT: Alterations in the lipid metabolism are linked to metabolic disorders such as insulin resistance (IR), obesity and type 2 diabetes (T2D). Regular exercise, particularly combined training (CT), is a well-known non-pharmacological treatment that combines aerobic (AT) and resistance (RT) training benefits. However, it is unclear whether moderate-intensity exercise without dietary intervention induces changes in lipid metabolism to promote a 'healthy lipidome'. OBJECTIVE: The study aimed to investigate the effect of 16 weeks of CT on plasma and white adipose tissue in both sexes, middle-aged subjects with normal weight, obesity and T2D using an ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) untargeted lipidomics approach. METHODS: Body composition, maximum oxygen consumption (VO2 max), strength, and biochemical markers were evaluated before and after the control/training period and correlated with lipid changes. CT consisted of 8 to 10 RT exercises, followed by 35 min of AT (45 -70% VO2 max), 3 times a week for 16 weeks. RESULTS: The CT significantly reduced the levels of saturated and monounsaturated fatty acid side-chains (SFA/MUFA) in sphingolipids, glycerolipids (GL) and glycerophospholipids (GP) as well as reducing fat mass, circumferences and IR. Increased levels of polyunsaturated fatty acids in GPs, and GLs were also observed, along with increased fat-free mass, VO2 max, and strength (all p < 0.05) after training. CONCLUSION: Our study stated that 16 weeks of moderate-intensity CT remodelled the lipid metabolism in OB, and T2D individuals, even without dietary intervention, establishing a link between exercise-modulated lipid markers and mechanisms that reduce IR and obesity-related comorbidities.

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.

Rho-Kinase Is Differentially Expressed in the Adipose Tissue of Rodent and Human in Response to Aging, Sex, and Acute Exercise.

White adipose tissue (WAT) controls energy storage, expenditure, and endocrine function. Rho-kinase (ROCK) is related to impaired thermogenesis, downregulation of preadipocyte differentiation, and adipokine production. Furthermore, WAT ROCK responds to metabolic stress from high-fat diets or diabetes. However, ROCK distribution in adipose depots and its response to aging and sex remain unclear. Thus, we aim to investigate ROCK function in adipose tissue of rodent and human in response to aging and sex. We observed specific differences in the ROCK1/2 distribution in inguinal WAT (ingWAT), perigonadal WAT (pgWAT), and brown adipose tissue of male and female rodents. However, ROCK2 expression was lower in female ingWAT compared with males, a fact that was not observed in the other depots. In the pgWAT and ingWAT of male and female rodents, ROCK activity increased during development. Moreover, middle-aged female rodents and humans showed downregulation in ROCK activity after acute physical exercise. Interestingly, ROCK levels were associated with several inflammatory markers both in rats and humans WAT (Nfkb1, Tnf, Il1b, Il6, and Mcp1). Induction of cell senescence by etoposide elevates ROCK activity in human preadipocytes; however, silencing ROCK1/2 demonstrates improvement in the inflammatory and cell senescence state. Using public databases, several pathways were strongly associated with ROCK modulation in WAT. In summary, WAT ROCK increases with development in association with inflammatory markers. Further, ROCK activity was attenuated by acute physical exercise, implicating it as a possible therapeutic target for metabolism improvement mediated by adipose tissue inflammatory state changes.

Synergistic effect rescue animal model from NASH caused by diet-inflammation inducer.

Excessive intake of pro-inflammatory fatty acids is related to the development of insulin resistance, impaired oxidative stress enzymes, and lipid disorders, leading to inflammation and development of non-alcoholic steatohepatitis (NASH). Diet and physical exercise are considered to prevent and treat metabolic disorders caused by chronic inflammatory states (responsible for insulin resistance and diabetes type 2) in individuals with obesity and nonalcoholic fatty liver diseases (NAFLD). Our investigation tested the hypothesis that Hass avocado oil, a monounsaturated fatty acid and a source of phytosterol, may improve liver and metabolic parameters without adverse effects when combined with physical exercise. Rats ingested a high-fat diet for seven weeks and were then subjected to more six weeks with a standard diet, Hass avocado-oil ingestion, and swimming. The intervention showed significantly improvements by synergistic effect between Hass avocado-oil and swimming exercise (P < 0.05), including improving adiponectin, leptin, and fasting blood glucose levels, alleviating insulin resistance, reducing serum TNF-α, improving glutathione enzyme levels, and decreasing lipotoxicity in the liver and blood and serum triacylglycerides in blood (P < 0.05). Liver tissue markers of apoptosis and necrosis such as CK-18 filaments and dimethylamine (DMA) were significantly higher in the intervention group (P < 0.05). We were unable to fully confirm our hypothesis. Although the synergistic effects between Hass avocado-oil and the swimming regimen offer a promising chance of recovering liver health by improving 10 health biological markers, we must not ignore the cellular damage due to apoptosis and necrosis in liver cells and DMA. The data on metabolomic profile and avocado-oil-treated livers highlight the need for further investigation.

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.

Effects of Different Exercise Types on Chrna7 and Chrfam7a Expression in Healthy Normal Weight and Overweight Type 2 Diabetic Adults.

Purpose: Considering that the CHRNA7 and CHRFAM7A genes can be modulated by acute or chronic inflammation, and exercise modulates inflammatory responses, the question that arises is whether physical exercise could exert any effect on the expression of these genes. Thus, the aim of this work is to identify the effects of different types of exercises on the expression of the CHRNA7, CHRFAM7A and tumor necrosis factor-α (TNF-α) in leukocytes of healthy normal weight (HNW), and overweight with type 2 diabetes (OT2D) individuals. Methods: 15 OT2D and 13 HNW participants (men and women, from 40 to 60 years old) performed in a randomized crossover design three exercise sessions: aerobic exercise (AE), resistance exercise (RE) and combined exercise (CE). Blood samples were collected at rest and post-60-min of the exercise sessions. The leukocytes were the analysis of the CHRNA7, CHRFAM7A and (TNF-α) gene expression. Results: At baseline, OT2D had higher CHRFAM7A and TNF-α expression compared to HNW. No statistical differences were observed between groups for CHRNA7; however, the HNW group presented almost twice as many subjects with the expression of this gene (24% vs. 49%). Post exercise, the CHRFAM7A increased in AE, RE and CE for HNW, and in AE and CE for OT2D. There was no significant difference for TNF-α and CHRNA7 expression between any type of exercise and group. Conclusions: Our study shows that OT2D individuals presented higher baseline expression of TNF-α and CHRFAM7A, besides evidence of decreased CHRNA7A expression in leukocytes when compared with HNW. On the other hand, acutely physical exercise induces increased CHRFAM7A expression, especially when the aerobic component is present.

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.

Comparison between frail and non-frail older adults' gut microbiota: A systematic review and meta-analysis.

BACKGROUND: Emerging evidence suggests that the intestinal microbiota (IM) undergoes remodelling as we age, and this impacts the ageing trajectory and mortality in older adults. The aim was to investigate IM diversity differences between frail and non-frail older adults by meta-analysing previous studies. METHODS: The protocol of this systematic review with meta-analysis was registered on PROSPERO (CRD42021276733). We searched for studies comparing IM diversity of frail and non-frail older adults indexed on PubMed, Embase, Cochrane, and Web of Science in November 2021. RESULTS: We included 11 studies with 1239 participants, of which 340 were meta-analysed. Frailty was defined by a variety of criteria (i.e. Fried Scale, European Consensus on Sarcopenia). There were no differences in the meta-analyses between the frail and non-frail groups for species richness index (SMD = -0.147; 95% CI = -0.394, 0.100; p = 0.243) and species diversity index (SMD = -0.033; 95% CI = -0.315, 0.250; p = 0.820). However, we identified almost 50 differences between frail and non-frail within the relative abundance of bacteria phyla, families, genera, and species in the primary studies. CONCLUSIONS: The evidence to prove that there are differences between frail and non-frail IM diversity by meta-analysis is still lacking. The present results suggest that further investigation into the role of specific bacteria, their function, and their influence on the physiopathology of frailty is needed.

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.

The effects of ageing, BMI and physical activity on blood IL-15 levels: A systematic review and meta-analyses.

AIM: The purpose of the study was to test the effect of ageing, BMI, physical activity and chronic exercise on IL-15 blood concentration by meta-analyses of the literature. METHODS: The search was performed on PubMed/MEDLINE, Web of Science, ProQuest, Embase and Cochrane databases. First meta-analysis compared blood IL-15 of healthy adults across three age groups (<35 years, 35-65 years, and >65 years), considering BMI as confounding factor; the second compared IL-15 levels between physically active and non-physically active individuals (cross-sectional studies); and the third tested the effect of chronic exercise interventions on blood IL-15 levels on participants of any age, sex, and health condition. RESULTS: From 2582 studies retrieved, 67 were selected for the three meta-analyses (age effect: 59; physical activity cross-sectional effect: 5; chronic exercise effect: 14). Older adults had lower blood IL-15 than young and middle-aged adults (5.30 pg/ml [4.76; 5.83]; 7.11 pg/ml [6.33; 7.88]; 7.10 pg/ml [5.55; 8.65], respectively). However, the subgroup of overweight older adults had higher IL-15 than young and middle aged overweight adults; Habitual physical activity did not affect blood IL-15 (standardized mean difference [SMD] 0.61 [-0.65; 1.88], p = 0.34); Chronic exercise reduced blood IL-15 in short-term interventions (<16 weeks) (SMD -0.14 [-0.27; -0.01], p = 0.04), but not studies of >16 weeks of intervention (SMD 0.44 [-0.26; 1.15], p = 0.22). CONCLUSION: The present meta-analyses highlight the complex interaction of age, BMI and physical activity on blood IL-15 and emphasize the need to take these factors into account when considering the role of this myokine in health throughout life.

Renal protection induced by physical exercise may be mediated by the irisin/AMPK axis in diabetic nephropathy.

In patients with diabetes, it has been suggested that physical exercise may reduce albuminuria and the progression of renal disease. However, the molecular mechanism by which physical exercise protects the kidney in diabetes remains poorly understood. The aim of the present study was to determine the contribution of muscle irisin secretion induced by aerobic physical exercise with the subsequent activation of AMPK for kidney protection under diabetic conditions. Aerobic physical exercise in rats protected the kidney in streptozotocin-induced diabetes. It reduced albuminuria, glomerular hypertrophy, and glomerular expression of collagen IV and fibronectin, as well as markers of kidney inflammation, when compared to sedentary diabetic rats. These effects were associated with elevation in muscle FNDC5/irisin and activity of AMPK in the diabetic kidney. However, the beneficial effects of exercise were lost when the diabetic rats were treated with CycloRGDyK, that in the bone it has been described as an irisin receptor blocker. In cultured human tubular (HK-2) cells, treatment with recombinant irisin counteracted the effect of high glucose in a dose-dependent manner. Irisin, per se, also activated AMPK in HK-2 cells. It is concluded that in diabetes, the renal protective effect of exercise may be mediated by the irisin/AMPK pathway.

Combined training increases thermogenic fat activity in patients with overweight and type 2 diabetes.

BACKGROUND: Exercise is an important strategy in the management of diabetes. Experimental studies have shown that exercise acts, at least in part, by inducing the production of myokines that improve metabolic control and activate brown/beige adipose tissue depots. Combined training (CT) is recommended by the major diabetes guidelines due to its metabolic and cardiovascular benefits, however, its impact on brown/beige adipose tissue activities has never been tested in humans with overweight and type 2 diabetes (T2D). Here, we evaluated the effects of 16-week combined training (CT) program on brown adipose tissue activity; browning and autophagy markers, and serum pro-thermogenic/inflammatory inducers in patients with overweight and T2D. METHODS: Thirty-four patients with overweight and T2D were assigned to either a control group (CG) or a combined training group (CTG) in a randomized and controlled study. Functional/fitness parameters, anthropometry/body composition parameters, blood hormone/biochemical parameters, thermogenic/autophagic gene expression in subcutaneous adipose tissue were evaluated before and at the end of the intervention. In addition, cold-induced 18-Fluoroxyglucose Positron Emission Computed Tomography (18F-FDG PET/CT) was performed in the training group before and after the end of the intervention. RESULTS: CT increased cervical/supraclavicular brown adipose tissue (BAT) thermogenic activity (p = 0.03) as well as in perirenal adipose tissue (p = 0.02). In addition, CT increased the expression of genes related to thermogenic profile (TMEM26: + 95%, p = 0.04; and EPSTI1: + 26%, p = 0.03) and decreased autophagic genes (ULK1: -15%, p = 0.04; LC3: -5%, p = 0.02; and ATG4: -22%, p < 0.001) in subcutaneous adipose tissue. There were positive correlations between Δ% BAT activity with Δ% of post training energy expenditure cold exposure, HDL-c, IL4, adiponectin, irisin, meteorin-like, and TMEM26 and ZIC1 genes, besides negative correlations with LDL-c, total cholesterol and C-reactive protein. CONCLUSION: This is the first evidence of the beneficial actions of CT on adipose tissue thermogenic activity in humans, and it adds important support for the recommendation of CT as a strategy in the management of diabetes.

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.

Inhibitory control after aerobic exercise with and without blood flow restriction in older adults / Controle inibitório após exercícios aeróbicos com e sem restrição do fluxo sanguíneo em idosos / Control inhibitorio después del ejercicio aeróbico con y sin restricción del flujo sanguíneo en adultos mayores

Introduction: Regular aerobic exercise (AE) can reduce the cognitive losses typically experienced with aging can be blunted by regular aerobic exercise (AE). AE also induces acute improvement of cognitive function among older adults; and AE practice with blood flow restriction (BFR) addss other benefits to elderly health, such as improvements in aerobic fitness, and increase in muscle mass and strength, however, it is not clear which EA protocol is more efficient to cognitive function. Objectives: Thus, the aimof this study was to compare AE protocols with and without BFR on the inhibitory control of the elderly. Methodology: Twenty-one elderly performed the Stroop test before and after three AE sessions in a repeated measure, cross-over design: AE with high load (70% VO2max), AE with low load (40% VO2max), and AE with blood flow restriction (AE-BFR) BFR (40% VO2max and 50% of BFR). Results and discussion: There was no significant effect from experimental sessions on cognitive function, assessed by inhibitory control in Stroop test. Perhaps, the load applied was not proper to stimulate cognitive function improvements, as seen the moderate loads have been more efficient to increase cerebral blood flow, among other physiological mechanisms encompassed. Final Considerations: Moreover, we observed very heterogeneous responses among individuals and sessions, suggesting that future research also considers biological individuality.

Introdução: As perdas cognitivas tipicamente experimentadas com o envelhecimento podem ser atenuadas por exercícios aeróbicos (EA) regulares. EA também induz melhora aguda da função cognitiva em idosos; e a prática de EA com restrição de fluxo sanguíneo (RFS) agrega outros benefícios à saúde do idoso, como melhorias na aptidão aeróbia e aumento da massa e força muscular. No entanto, não está claro qual protocolo de EA é mais eficaz para a funcao cognitiva. Objetivos: Assim, o objetivo deste estudo foi comparar diferentes protocolos de EA com e sem RFS no controle inibitório de idosos. Metodologia: Vinte e um idosos realizaram o teste de Stroop antes e após três sessões de EA em medida repetida, desenho cruzado: EA com alta carga (70% VO2máx), EA com baixa carga (40% VO2máx) e EA com RFS (40% VO2máx e 50% do RFS). Resultados e discussão: Não houve efeito significativo das sessões experimentais na função cognitiva avaliada pelo controle inibitório no Stroop Test. Talvez, as cargas aplicadas não tenham sido adequadas para estimular melhorias no controle inibitório, visto que as cargas moderadas têm sido mais eficientes para aumentar o fluxo sanguíneo cerebral, entre outros mecanismos fisiológicos Considerações Finais: Além disso, observamos respostas bastante heterogêneas entre indivíduos e sessões, sugerindo que pesquisas futuras considere também a individualidade biológica.

Introducción: El ejercicio aeróbico regular (EA) puede reducir la perdida cognitiva tipicamente experimentada durante el envejecimiento. EA puede tambien inducir mejora en la funcion cognitiva entre adultos mayores, ademas, la practica de resticcion de flujo sanguíneo (RFS) agrega otros beneficios para la salud en los ancianos, así como mejoras en la aptitud aeróbica, aumento de la masa muscular y la fuerza, sin embargo, no está claro qué protocolo de EA es más eficiente para la función cognitiva. Objetivos: El objetivo de este estudio fue comparar los protocolos de EA con y sin RFS en el control inhibitorio de los ancianos. Metodología: Veintiún ancianos realizaron la prueba de Stroop antes y después de tres sesiones de EA en medida repetida, diseño cruzado: EA con carga alta (70% VO2max), EA con carga baja (40% VO2max) y EA con restricción del flujo sanguíneo (EA-RFS) RFS (40% VO2max y 50% de RFS). Resultados y discusión: No hubo efecto significativo de las sesiones experimentales sobre la función cognitiva, evaluada por el control inhibitorio en la prueba de Stroop. Quizás, la carga aplicada no fue la adecuada para estimular mejoras en la función cognitiva, ya que las cargas moderadas han sido más eficientes para aumentar el flujo sanguíneo cerebral, entre otros mecanismos fisiológicos englobados. Consideraciones finales: Además, nosotros observamos respuestas muy heterogéneas entre individuos y sesiones, lo que sugiere que para futuras investigaciones también se debe considerar la variabilidad biológica.