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.

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.

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.

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.

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 Physical Training Increases Plasma Brain-Derived Neurotropic Factor Levels, But Not Irisin in People Living with HIV/AIDS.

This study evaluated plasma levels of brain-derived neurotropic factor (BDNF), irisin, and lactate in people living with HIV/AIDS who completed a combined physical training program. Nineteen HIV+ participants (age: 39.60 ± 10.96 years; carrier time: 7.75 ± 7.88 years; time of ART: 6.41 ± 5.93 years) performed strength/aerobic training (combined physical training) in the same session for 8 weeks and levels of BDNF, irisin, and lactate were assessed. BDNF (pg/mL) was higher post-CPT (Pre: 1258.73 ± 372.30; Post: 1504.17 ± 322.30; p < 0.001). Irisin (ng/mL) showed no change (Pre: 115.61 ± 72.41; Post: 125.87 ± 81.14; p = 0.973). There was positive correlation between irisin and lactate (mmol/L) pre (r = 0.55, p = 0.04), and lactate values were higher in the group with the highest value of irisin (3.65 ± 0.69 × 2.82 ± 0.59, p = 0.02). Combined physical training results in increased basal BDNF in people living with HIV/AIDS, this finding suggests that increased concentration of BDNF may be associated with decreased chances of developing cognitive disorders or HIV-associated dementia. Further studies involving molecular mechanisms on this subject are necessary.

Acute/Chronic Responses of Combined Training on Serum Pro-thermogenic/Anti-inflammatory Inducers and Its Relation With Fed and Fasting State in Overweight Type 2 Diabetic Individuals.

Concentrations of pro-thermogenic/anti-inflammatory inductors are influenced by fed/fasting, sedentary/trained states, and metabolic pattern. However, there is a lack of information on the interactions of these conditions, especially in humans. Thus, the present study aimed to evaluate the chronic and acute training responses as well as the fed/fasted states of serum pro-thermogenic/anti-inflammatory inducers in overweight type 2 diabetics individuals. Fifteen individuals with type 2 diabetes [body mass index (BMI): 29.61 ± 3.60 kg/m2; age: 50.67 ± 3.97 years] participated in the study. In the pre- and post-experimental periods, baseline clinical parameters analyses were performed. Pro-thermogenic/anti-inflammatory inductors were evaluated pre/post-baseline and before, shortly after, and after 30' and 60' in the first and last sessions of a 16-week combined training (CT) period. These inducers were also compared for fasting and feeding before and after the training period. CT has improved baseline physical fitness, metabolic pattern, and it has also increased interleukin (IL)33 and FNDC5/irisin. In the first training session, there was a decrease in IL4, IL13, and IL33, besides an increase in FNDC5/irisin, and natriuretic peptides. In the last training session, there was an increase in natriuretic peptides and bone morphogenic protein 4 (BMP4). Differences in responses between the first and last training sessions were observed at certain post-session times for IL4, IL33, and natriuretic peptides, always with higher concentrations occurring in the last session. In evaluating the area under the curve (AUC) of the first and last training session, FNDC5/irisin, natriuretics peptides, and meteorin-like showed increased areas in the last training session. The pre-training fed state showed an increase in IL4 and IL33, while in fasting there was an increase in meteorin-like, natriuretic peptides, and FNDC5/irisin. In the post-training, IL4, IL13, and IL33 were increased in the fed state, while meteorin-like, natriuretic peptides, and FNDC5/irisin remained increased in the fast. Adaptation to physical training and a better metabolic pattern favor an improvement in the acute secretory pattern in part of pro-thermogenic and anti-inflammatory substances analyzed. The fed and fasting states also interfere differently in these substances, where fasting interferes with the increase of myokines, while the fed state induces an increase in interleukins. Clinical Trial Registration: [http://www.ensaiosclinicos.gov.br/rg/RBR-62n5qn/], identifier [U1111-1202-1476].

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

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.

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 (µg/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 (µg/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 (Δ%) in levels of FNDC5/irisin and Δ% glucose, Δ% total cholesterol, Δ% triglycerides and Δ% waist circumference, in addition to a positive relation with Δ% 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 humans.

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.

Ciclismo Indoor como Modalidade de Exercício Físico em Programa Multidisciplinar para o Tratamento do Excesso de Peso em Adolescentes: Influência nos Parâmetros Antropométricos e Funcionais / Indoor Cycling as a Physical Exercise Modality in a Multidisciplinary Program for the Treatment of Overweight in Adolescents: Influence on Anthropometric and Functional Parameters

Os objetivos do presente estudo foram avaliar osefeitos de 24 semanas de um programa multidisciplinarcomposto por ciclismo indoor sobre parâmetrosantropométricos e funcionais de adolescentes com excessode peso, e o comportamento da frequência cardíaca destesindivíduos durante a prática desta modalidade. Material eMétodos: Participaram 34 adolescentes de ambos os sexos,com sobrepeso ou obesidade e idade entre 11 e 16 anos(13,20 ± 1,7). Mensuraram-se no início, três e seis meses dotratamento: peso (kg), estatura (cm), consumo de oxigêniodireto (VO2pico) em teste máximo em cicloergômetro e calculouseo índice de massa corporal (IMC). O CI prescrito teveintensidade progressiva (1º mês, 35 a 55%; 2º mês, 45 a65% e do 3º ao 6º mês, 55 a 75% da FCreserva), 3 x semana, 50minutos. Resultados: Nos três primeiros meses, a FCrepousodiminuiu significativamente (p<0,05) tanto nos meninos (81±9para 72±8 bpm) como nas meninas (81±11 para 74±9 bpm),no entanto o IMC diminuiu somente nos meninos (27,7± 1,7para 25,5±1,9 kg/m2, p<0,05). Os meninos aumentaram oVO2pico corrigido pela massa corporal (32,7±6,6 para 36,9±6,1kg.ml-1.min-1, p<0,05) dos três aos seis meses. Conclusão: OCI apresentou-se como uma alternativa nos EF sem asustentação do peso corporal, contribuindo para a diminuiçãodo IMC e aumento do VO2pico, principalmente nos meninos...

To evaluate the effects of 24 weeks of amultidisciplinary program consisting of indoor cycling onanthropometric and functional parameters of overweightadolescents, as well as the heart rate behavior of theseindividuals during the practice of this modality. Material andMethods: A total of 34 overweight and obese adolescents ofboth sexes aged between 11 and 16 years (13.20 ± 1.7)participated in this study. In the beginning of the treatmentand 3 and 6 months after that, the following elements weremeasured: weight (kg), height (cm) and direct peak oxygenuptake (VO2peak) in maximum exercise test in a cycloergometer;then, body mass index (BMI) was calculated. Indoor cycling(IC) sessions had progressive intensity and happened 3 timesa week, lasting 50 minutes. Results: In the first three months,the resting HR decreased significantly (p<0.05) in both boys(81±9 to 72±8 bpm) and girls (81±11 to 74±9 bpm). However,BMI decreased only in boys (7.7±1.7 to 25.5±1.9 kg/m2,p<0.05). The boys increased their VO2peak, corrected for bodymass, (32.7±6.6 to 36.9±6.1 kg.ml-1.min-1, p<0.05) from the 3rdto the 6th month. Conclusion: Indoor cycling has representedan alternative of physical exercise without sustaining bodyweight, contributing to the decrease of BMI and increase ofVO2peak, mainly in boys...