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.

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.

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.

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.

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.

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.

Effects of combined training on total ghrelin and tumor necrosis factor-α in obese middle-aged men

Abstract AIMS The aim of the present study was to investigate the effects of combined training (CT) on total ghrelin and tumor necrosis factor-α (TNF-α) levels in obese middle-aged individuals. METHODS Twenty two obese middle-aged men (49.32 ± 5.74 years; Body mass index: 30.88 ± 1.64 kg/m²) were randomly assigned to a combined training group (CTG, n = 12) or a control group (CG, n = 10). The CT consisted of aerobic (50-85% of VO2peak) and resistance (6-10 RM) training performed three times per week, 60 min per session for 24 weeks. The anthropometric measurements, cardiorespiratory test (VO2peak), maximal strength assessment (1RM) and plasma concentrations of total ghrelin and TNF-α were determined before (Pre) and after 24 weeks (Post) of the experimental period. RESULTS Decreases were found in body fat percentage (Δ% -19.8) and waist circumference (Δ% -2.8) for CTG at the Post moment as compared to the Pre moment. In addition, the CTG demonstrated increases for VO2peak (Δ% 13.4) and for 1-RM of bench press (Δ% 78.1), leg press (Δ% 22.3) and arm curl (Δ% 19.3) at the Post moment as compared to the Pre moment. However, total ghrelin levels remained unchanged for CTG and CG after the experimental period, while TNF-α levels increased for CG (p ≤ 0.05). CONCLUSION the CT protocol performed was not effective in repairing total ghrelin levels and was not correlated with changes in the TNF-α; however, the exercise training was able to improve body composition and functional capabilities and contained the worsening of systemic inflammation associated to obesity.

Metabolomics Approach in the Investigation of Metabolic Changes in Obese Men after 24 Weeks of Combined Training.

Obesity is associated with comorbidities related to metabolic disorders due to excess of adipose tissue. Physical exercise has a major role in the prevention of obesity. Combined training (CT), in particular, has been shown to improve markers of health. In this study, we used 1H NMR-based metabolomics to investigate changes in the metabolism of obese men after 24 weeks of CT. Twenty-two obese (body mass index 31 ± 1.4 kg/m2), middle-aged men (48.2 ± 6.1 years) were randomly assigned to a control group (CG, n = 11) or CT group (n = 11). The CT was performed three times a week (resistance and aerobic training) for 24 weeks. Blood samples were collected before and after experimental period. There was an improvement in body composition and physical fitness indices after CT training. Multivariate PCA and PLS-DA models showed a distinct separation between groups. Twenty metabolites with importance for projection (VIP) >1.0 were identified, and four were classified as best discriminators (tyrosine, 2-oxoisocaproate, histidine, pyruvate). Some metabolites were correlated with strength, VO2 peak, fat and lean body mass, waist circumference, and insulin. In conclusion, 24 weeks of CT was effective for functional improvements and metabolic changes in obese middle-aged men.