Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk

Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. Subjects and methods: On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. Results: The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r −0.46, p = 0.04), neck circumference (r −0.51, p = 0.02), free fat mass (r −0.49, p = 0.02), triglycerides (r −0.43, p = 0.05) and risk of developing T2DM (r −0.61, p = 0.04) were observed. Conclusions: These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance61652453

Association of skeletal muscle and serum metabolites with maximum power output gains in response to continuous endurance or high-intensity interval training programs: The TIMES study - A randomized controlled trial

Recent studies have begun to identify the molecular determinants of inter-individual variability of cardiorespiratory fitness (CRF) in response to exercise training programs. However, we still have an incomplete picture of the molecular mechanisms underlying trainability in response to exercise training. Objective We investigated baseline serum and skeletal muscle metabolomics profile and its associations with maximal power output (MPO) gains in response to 8-week of continuous endurance training (ET) and high-intensity interval training (HIIT) programs matched for total units of exercise performed (the TIMES study). Methods Eighty healthy sedentary young adult males were randomized to one of three groups and 70 were defined as completers (> 90% of sessions): ET (n = 30), HIIT (n = 30) and control (CO, n = 10). For the CO, participants were asked to not exercise for 8 weeks. Serum and skeletal muscle samples were analyzed by 1H-NMR spectroscopy. The targeted screens yielded 43 serum and 70 muscle reproducible metabolites (intraclass > 0.75; coefficient of variation < 25%). Associations of baseline metabolites with MPO trainability were explored within each training program via three analytical strategies: (1) correlations with gains in MPO; (2) differences between high and low responders to ET and HIIT; and (3) metabolites contributions to the most significant pathways related to gains in MPO. The significance level was set at P < 0.01 or false discovery rate of 0.1. Results The exercise programs generated similar gains in MPO (ET = 21.4 +/- 8.0%; HIIT = 24.3 +/- 8.5%). MPO associated baseline metabolites supported by all three levels of evidence were: serum glycerol, muscle alanine, proline, threonine, creatinine, AMP and pyruvate for ET, and serum lysine, phenylalanine, creatine, and muscle glycolate for HIIT. The most common pathways suggested by the metabolite profiles were aminoacyl-tRNA biosynthesis, and carbohydrate and amino acid metabolism. Conclusion We suggest that MPO gains in both programs are potentially associated with metabolites indicative of baseline amino acid and translation processes with additional evidence for carbohydrate metabolism in ET142CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP149201/2015-0; 140302/2018-288881.135219/2016-012018/24108-9; 2016/057417Sao Paulo Research Foundation (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/24108-9, 2016/057417]; Support Fund for Teaching, Research and Extension (FAEPEX) [2021/16]; National Council for Scientific and Technological Development (CNPq)National Council for Scientific and Technological Development (CNPq) [149201/2015-0, 140302/2018-2]; Coordination for the Improvement of Higher Education Personnel (PDSE-CAPES) [88881.135219/2016-01]; COBRE center grant from the U.S.A. National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH8 1P30GM118430-02]; NIH-funded COBRE grantUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [NIH 8P30GM118430-01]; National Institute of General Medical Sciences of the National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [2 U54 GM104940

Metabolomics and Exercise: possibilities and perspectives

Abstract Aim This review aimed to provide an overview of the publications using metabolomics in research with physical exercises and to demonstrate how researchers have been applying this approach. Methods A systematic search in the databases Web of Science, SCOPUS and PubMed was performed, with the key words: "metabolomics" OR "metabonomics" and with "metabolomics" OR "metabonomics" AND "exercise" in the title or abstract of the articles. The search period was from 2000 to 2016. Forty-four original articles were selected. The studies found were separated into four categories: metabolic responses to physical exercise, supplementation and physical exercise, sports performance, and physical exercise related to diseases. Results It was possible to observe the exponential growth of the use of this approach in Sports and Health Sciences, and the four sub-fields towards which these researches involving exercise are directed, enabling a more comprehensive characterization of different metabolic profiles, as well as their study for identifying new biomarkers related to physical exercise. Conclusions The possibilities of using metabolomics approach are increasing in the fields of Health Sciences, Sports, and Physical Activity. The experimental design of the study is essential to take advantage of this tool and be able to answer questions in the metabolism comprehension

<b>MODERATE-INTENSITY COMBINED TRAINING INDUCES LIPIDOMIC CHANGES IN INDIVIDUALS WITH OBESITY AND TYPE 2 DIABETES</b>

Abstract: 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.</p

Combined training, FNDC5/irisin levels and metabolic markers in obese men: A randomised controlled trial

The effects of training on FNDC5/irisin and its association with fitness and metabolic marker improvements induced by training have been poorly investigated in humans. Thus, the present study assessed the effects of combined training (CT) on FNDC5/irisin levels, metabolic markers and fitness adaptations in obese men. Middle-age obese men (age 49.13 +/- 5.75, body mass index (BMI) 30.86 +/- 1.63) were randomly distributed in the CT group (n = 12) and control group (CG n = 10). The CT consisted of strength followed by aerobic training, 3 times/week, for 24 weeks. Body composition, physical fitness, plasma FNDC5/irisin, biochemical markers and metabolic scores/index were evaluated. CT maintained FNDC5/irisin levels (mu g/mL) (pre: 4.15 +/- 0.32, post: 4.21 +/- 0.32; p = .96) and improved body composition, metabolic and physical fitness markers. In the CG, decreased FNDC5/irisin (mu g/mL) (pre: 4.36 +/- 0.23, post: 3.57 +/- 0.94; p = .01) and reduced strength (supine exercise/kg) (pre: 71 +/- 14.7, post: 60.1 +/- 14.05; p < .01) were observed, along with a trend to increase HOMA-IR (pre: 2.63 +/- 1.11, post: 3.14 +/- 1.27; p = .07) and other indicators of metabolic deterioration. An inverse correlation was found between the change (Delta%) in levels of FNDC5/irisin and Delta% glucose,Delta% total cholesterol,Delta% triglycerides and Delta% waist circumference, in addition to a positive relation with Delta% muscle strength. In conclusion, CT maintained FNDC5/irisin levels and provided metabolic and fitness benefits. The correlation between FNDC5/irisin changes and metabolic parameters, as well as the FNDC5/irisin reduction associated with fitness and metabolic worsening in the CG, suggests a relationship between FNDC5/irisin and a healthy metabolic status in humans175629637FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP11/09446-

Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk

FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. Subjects and methods: On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNF&#945;), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. Results: The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p &lt; 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r &#8722;0.46, p = 0.04), neck circumference (r &#8722;0.51, p = 0.02), free fat mass (r &#8722;0.49, p = 0.02), triglycerides (r &#8722;0.43, p = 0.05) and risk of developing T2DM (r &#8722;0.61, p = 0.04) were observed. Conclusions: These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance616524533FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2015/13229-

Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk

ABSTRACT Objective: Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. Subjects and methods: On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. Results: The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r −0.46, p = 0.04), neck circumference (r −0.51, p = 0.02), free fat mass (r −0.49, p = 0.02), triglycerides (r −0.43, p = 0.05) and risk of developing T2DM (r −0.61, p = 0.04) were observed. Conclusions: These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance

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