Interdisciplinary Therapy Improves the Mediators of Inflammation and Cardiovascular Risk in Adolescents with Obesity.

Obesity is associated with inflammation and an increased risk of cardiovascular disease and premature mortality, as well as a range of other conditions. Obesity is a growing global problem, not only in adults, but also in children and adolescents. Therefore, the present study aimed to assess the effects of a one-year interdisciplinary intervention on the cardiometabolic and inflammatory profiles of adolescents with obesity. Twenty-two adolescents completed the intervention, which included clinical, nutritional, psychological and physical exercise counselling. Body composition, and metabolic, inflammatory, and cardiovascular risk biomarkers were analyzed before and after one year of intervention. Visceral and subcutaneous fat were determined ultrasonographically. The homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) equation were used to estimate insulin resistance and insulin sensitivity, respectively. A reduction in body mass, adiposity, glucose, and insulin and an improved lipid profile were observed after the therapy. Hyperleptinemia was reduced from 77.3% to 36.4%. Plasminogen activator inhibitor-1 (PAI-1), intercellular adhesion molecule 1 (ICAM-1), leptin, the leptin/adiponectin ratio, and the adiponectin/leptin ratio were also significantly improved. Metabolic changes were associated with a reduction in visceral fat and waist circumference, and adiponectin and the leptin/adiponectin ratio were associated with HOMA-IR. The interdisciplinary therapy promoted improvements in hyperleptinemia and metabolic, inflammatory, and cardiovascular biomarkers.

The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity. / O Papel dos Níveis Séricos de ANP na Perda de Peso, Risco Cardiometabólico e Composição Corporal de Adolescentes com Obesidade Submetidos a Terapia Interdisciplinar.

BACKGROUND: The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations. OBJECTIVE: To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity. METHODS: 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels. RESULTS: Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only. CONCLUSION: This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.

FUNDAMENTO: A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas. OBJETIVO: Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade. MÉTODOS: 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19). RESULTADOS: Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento. CONCLUSÃO: Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.

O Papel dos Níveis Séricos de ANP na Perda de Peso, Risco Cardiometabólico e Composição Corporal de Adolescentes com Obesidade Submetidos a Terapia Interdisciplinar / The Role of ANP Level Response in Interdisciplinary Weight Loss Therapy on Cardiometabolic Risk and Body Composition in Adolescents with Obesity

Resumo Fundamento A ação do peptídeo natriurético atrial (ANP) na natriurese, diurese e vasodilatação, resistência à insulina, fígado, rim e tecido adiposo pode contribuir para o desenvolvimento metabólico e cardiovascular saudável. Embora o nível circulante de ANP seja reduzido em pacientes com obesidade, sua resposta à perda de peso ainda é pouco explorada em populações pediátricas. Objetivo Avaliar os efeitos das variações do ANP em resposta à intervenção interdisciplinar para perda de peso na Síndrome Metabólica (SMet) e nos riscos cardiometabólicos em adolescentes com obesidade. Métodos 73 adolescentes com obesidade participaram de uma terapia interdisciplinar para perda de peso de 20 semanas, incluindo uma abordagem clínica, nutricional, psicológica e de exercícios físicos. A composição corporal, análises bioquímicas e pressão sanguínea foram avaliadas. A SMet foi classificada de acordo com a Federação Internacional de Diabetes (IDF) (2007). Após o tratamento, os voluntários foram divididos de acordo com os níveis de plasma do ANP aumento (n=31) ou ANP redução (n=19). Resultados Ambos os grupos apresentaram redução significativa de peso corporal, índice de massa corporal (IMC) e circunferências de cintura, pescoço e quadril (CC, CP e CQ, respectivamente), e aumento da massa livre de gordura (MLG). É interessante observar que houve uma redução significativa na gordura corporal, na razão de TG/HDL-c e na prevalência de SMet (de 23% para 6%) somente no grupo com ANP aumento. Conclusão Este estudo sugere que o aumento nos níveis séricos de ANP após a terapia para perda de peso pode estar associado a melhorias nos riscos cardiometabólicos e na prevalência reduzida de SMet em adolescentes com obesidade.

Abstract Background The action of atrial natriuretic peptide (ANP) on natriuresis, diuresis and vasodilatation, insulin resistance, liver, kidney, and adipose tissue may contribute to the healthy metabolic and cardiovascular development. Even though the circulating level of ANP is reduced in patients with obesity, its response to weight loss remains poorly explored in pediatric populations. Objective To evaluate the effects of ANP variations in response to interdisciplinary weight loss intervention on metabolic syndrome (MetS) and cardiometabolic risks in adolescents with obesity. Methods 73 adolescents with obesity attended a 20-week clinical interdisciplinary weight loss therapy including clinical, nutritional, psychological and exercise training approach. Body composition, biochemical analyses and blood pressure were evaluated. MetS was classified according to the International Diabetes Federation (IDF) (2007). After the treatment, volunteers were divided according to Increasing (n=31) or Decreasing (n=19) ANP plasma levels. Results Both groups present significant reduction of body weight, Body Mass Index (BMI), waist, neck and hip circumferences (WC, NC and HC, respectively) and increasing fat-free mass (FFM). Interestingly, a significant reduction in body fat, TG/HDL-c ratio and MetS prevalence (from 23% to 6%) was observed in the Increased ANP group only. Conclusion This study suggests that an increase in ANP serum levels after weight loss therapy could be associated with improvements in cardiometabolic risks and the reduced prevalence of MetS in adolescents with obesity.

Semi-intensive and Intensive Interdisciplinary Treatments Have Similar Effects on Metabolic Syndrome and Selected Inflammatory Markers in Adolescents with Obesity.

BACKGROUND: The purpose of the present study was to compare the impact of semi-intensive and intensive interdisciplinary weight-loss therapies on the treatment of metabolic syndrome (MS) and selected inflammatory markers in adolescents with obesity. METHODS: The study included 166 adolescents enrolled in two groups for 22 weeks: the intensive group (in-person aerobic and resistance exercise three times a week, and psychological and nutritional counselling once a week), or the semi-intensive group (six in-person exercise orientation meetings and six in-person psychological support sessions with an online nutritional and exercise program). Anthropometric parameters, blood pressure, fasting glucose, insulin, lipid profile, triglycerides (TG), leptin and adiponectin were assessed before and after the interventions. RESULTS: Body weight and waist circumference decreased in both groups (P<0.001) and large effect sizes (η2= 0.586 and η2=0.465, respectively) were noted. Significant time and group interactions were found (P=0.001) with medium effect sizes (η2=0.095 and η2=0.105, respectively). The prevalence of MS decreased from 27.9% to 13.1% (P=0.012) and 29.4% to 5.9% (P=0.004) in the semi-intensive and intensive groups, respectively. All MS risk factors decreased significantly over time (P<0.001) and a significant time*group interaction was observed (P<0.05), except for fasting TG (P=0.832) and glucose (P=0.128, η2=0.021). CONCLUSION: The results suggested that both approaches promoted significant clinical improvement in the condition of adolescents with MS and reduced associated risk factors. Studies that consider the cost effectiveness of both treatments are still needed to determine whether semi-intensive care, with its lower financial costs, may be a suitable option to treat obesity and MS in adolescents with obesity.

Effects of an interdisciplinary weight loss program on fibroblast growth factor 21 and inflammatory biomarkers in women with overweight and obesity

ABSTRACT Objective: To investigate the effects of an interdisciplinary intervention on biomarkers of inflammation and their relationship with fibroblast growth factor 21 (FGF21) concentrations in women with overweight and obesity. Subjects and methods: Thirty-one women were enrolled in a 12-week interdisciplinary weight loss program delivered by a team comprising an endocrinologist, nutritionist and exercise physiologist. Body composition; anthropometric measures; metabolic and inflammatory markers including adiponectin, leptin, and atrial natriuretic peptide (ANP) were assessed at baseline and post-therapy. The homeostasis model assessment of insulin resistance (HOMA-IR) and the homeostasis model assessment of adiponectin (HOMA-AD) were calculated. The participants were divided into two groups: those with increased FGF21, and those with decreased FGF21. Results: The sample comprised women aged 32 ± 5 years with a body mass index of 33.64 ± 3.49 kg/m2. Body weight, waist circumference and leptin concentration were decreased in the whole sample after therapy. However, only the group with an increase in FGF21 concentration presented significant improvements in adiponectin concentration and adiponectin/leptin ratio. Moreover, although there was a reduction of leptin in both groups, it was greater in the increased FGF21 groups. There was a reduction in ANP in the decreased FGF21 group. Conclusions: Changes in FGF21 concentrations were different among the women participating in the weight loss program, with some having increased levels and some reduced levels. Furthermore, improvements in adiponectin and the adiponectin/leptin ratio were found only in the group with increased FGF21 concentration.

Adipocytokine and appetite-regulating hormone response to weight loss in adolescents with obesity: Impact of weight loss magnitude.

OBJECTIVE: The aim of this study was to investigate the association between the magnitude of weight loss (WL) and serum concentrations of the main adipocytokines and appetite-regulating hormones in adolescents with obesity. METHODS: After completion of informed consent,108 adolescents with obesity (14-19 y of age; postpubertal) were submitted to clinical, nutritional, psychological, physical exercise, and physiotherapy support for 1 y. Body composition (BC) and plasma levels of neuropeptides (neuropeptide Y [NPY], agouti-related peptide [AgRP], and α-melanocyte-stimulating hormone [α-MSH]) and leptin were measured at baseline and post-intervention. RESULTS: After therapy, adolescents who lost <10% body weight and <10% body weight (were compared. Both groups presented improvements in BC and reduced leptin. The Δα-MSH, Δα-MSH/AgRP ratio, and Δα-MSH/NPY ratio were lower and AgRP and NPY variations were higher in the low weight loss group. The leptin concentration was close to normal in the high weight loss only. The ΔWeight, Δα-MSH and Δleptin were associated with body fat loss by multiple linear regressions for all samples. CONCLUSION: Weight loss >10% seems to reverse obesity-induced hyperleptinemia while stabilizing the neuropeptides that control appetite in adolescents with obesity. We were able to produce a prognostic mathematical model to predict body fat loss using weight, leptin, and α-MSH variations.

Effects of photobiomodulation and a physical exercise program on the expression of inflammatory and cartilage degradation biomarkers and functional capacity in women with knee osteoarthritis: a randomized blinded study

Abstract Background: The knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA. Methods: Forty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1β, IL-6, IL-8, IL-10 e TNF-α, and CTX-II). Results: An increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1β concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups. Conclusion: Our data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals. Trial registration: ReBEC (RBR-7t6nzr).

Acute Photobiomodulation Effects Through a Cluster Device on Skeletal Muscle Fatigue of Biceps Brachii in Young and Healthy Males: A Randomized Double-Blind Session.

Objective: The aim of this study was to investigate and compare the acute effects of red and infrared photobiomodulation (PBM) using a cluster device on biceps brachii muscle fatigue in young and healthy males. Background: Vigorous physical activity could lead to muscle fatigue, which compromises motor control and muscle strength and consequently impairs performance. The positive effects of PBM in reducing fatigue onset have been highlighted. However, the better wavelength with cluster devices is not yet established. Methods: A randomized double-blind session was used. Thirty-two young and healthy males were randomized into the control group (CG), red PBM group (RPG), and infrared PBM group (IPG). A PBM cluster device [7 visible diodes (630 nm), 7 infrared diodes (850 nm), 100 mW/diode, 2 W/cm2 power density, 91 J/cm2 energy density, 4 J per point, 28 J total energy, and 40 sec] was applied after muscle fatigue. Muscle fatigue was analyzed by surface electromyography (EMG) recorded from the long head of biceps brachii, blood lactate concentration, and evaluation of the rate of perceived exertion (RPE) using the Borg Scale. The fatigue protocol consisted of a maximum voluntary isotonic contraction of elbow flexion-extension with 75% of one-repetition maximum until exhaustion. The Borg Scale was applied before and at the end of the experiment to measure the RPE. The electromyography fatigue index (EMGFI) was calculated by windows of median frequency from EMG data. Results: EMGFI, blood lactate concentration, and RPE showed no intergroup statistical difference, except the EMGFI delta value that showed a difference between IPG and CG, with a greater value in the CG. However, intragroup comparisons showed that EMGFI decreased in the CG and RPE and lactate concentration increased significantly in all groups. Conclusions: There was no difference between red and infrared PBM in reduction of biceps brachii fatigue. However, the EMGFI delta value was greater in the IPG compared with the CG, suggesting that infrared can be more effective in reducing biceps brachii fatigue.

Higher increase degree of FGF21 post long-term interdisciplinary weight loss therapy preserves the free fat mass and rest metabolic rate in adolescents with obesity

ABSTRACT Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.

Interdisciplinary therapy had positive effects on inflammatory state, mediated by leptin, adiponectin, and quality of diet in obese women / La terapia interdisciplinaria tuvo efectos positivos en el estado inflamatorio, mediado por la leptina, la adiponectina y la calidad de la dieta en mujeres obesas

BACKGROUND: obesity is a chronic disease associated with inadequate eating habits and reduced levels of physical activity. Because of obesity, the risk for comorbidities is increased, especially for cardiovascular diseases, insulin resistance, and increased pro-inflammatory factors. The aim of the present investigation was to analyze potential correlations between pro/anti-inflammatory adipokines, glycemic index, and other markers of diet quality using a metabolic profile in women undergoing interdisciplinary weight loss therapy. METHODS: thirty-two women with obesity were enrolled in a 12-week program of interdisciplinary therapy combining a clinical, nutritional, and physical exercise approach. Body composition, quality of diet, metabolic profile, and pro/anti-inflammatory adipokines were analyzed. RESULTS: the therapy showed to be effective in reducing body weight (from 93.16 ± 16.96 to 88.36 ± 16.23; p = 0.0000001), body mass index (from 34.01 ± 4.00 to 32.29 ± 3.96; p = 0.0000001), and body fat (from 38.25 ± 5.05 to 36.13 ± 5; p = 0.0000001). There was also an improvement in lipid profile, including total cholesterol (from 196.16 ± 34.78 to 183.53 ± 43.15; p = 0.001), non-HDL-cholesterol (from 142 ± 30.05 to 1333.69 ± 35.41; p = 0.01), VLDL-cholesterol (from 27.13 ± 12.4 to 22.06 ± 8.55; p = 0.002), triglycerides (from 135.88 ± 61.21 to 110.75 ± 43.09; p = 0.002) and glucose metabolism, including glucose (from 97.13 ± 10.43 to 92.6 ± 6.6; p = 0.004), and insulin (from 13.05 ± 5.54 to 11.29 ± 4.85; p = 0.03). As for food intake, there was a decrease in calorie consumption (from 1991.45 ± 677.78 to 1468.88 ± 390.56; p = 0.002), carbohydrates (from 50.37 ± 6 to 47.04 ± 8.67; p = 0.04), lipids (from 31.83 ± 5.53 to 30.37 ± 7.04; p = 0.3), and glycemic load (from 80.53 ± 39.88 to 54.79 ± 23.69; p = 0.02), and an increased consumption of proteins (from 18.3 ± 2.39 to 22.89 ± 4.9; p = 0.002). Positive correlations were demonstrated between insulin concentration and waist circumference (r = 0.82; p = 0.003); leptin and body fat and abdominal circumference (r = 0.74; p = 0.01); and LDL-cholesterol fraction and total cholesterol consumption (r = 0.69; p = 0.027). Negative correlations were demonstrated between leptin and monosaturated fat consumption (r = -0.71; p = 0.02); and adiponectin and liver enzyme GGT levels (r = -0.65; p = 0.04). CONCLUSIONS: interdisciplinary therapy had positive effects on inflammatory state, mediated by leptin, adiponectin, and quality of diet. Our findings suggest the effectiveness and clinical relevance of the interdisciplinary clinical therapy applied for obesity

INTRODUCCIÓN: la obesidad es una enfermedad crónica asociada con hábitos alimentarios inadecuados y niveles reducidos de actividad física. Debido a la obesidad, el riesgo de comorbilidad aumenta, especialmente el de las enfermedades cardiovasculares, la resistencia a la insulina y el aumento de los factores proinflamatorios. El objetivo de la presente investigación fue analizar las posibles correlaciones entre las adipocinas pro/antiinflamatorias, el índice glucémico y otros marcadores de calidad de la dieta con el perfil metabólico en mujeres sometidas a terapia interdisciplinaria para perder peso. MÉTODOS: treinta y dos mujeres con obesidad participaron en 12 semanas de terapia interdisciplinaria en la que se combinaron los enfoques clínico, nutricional y de ejercicio físico. Se analizaron la composición corporal, la calidad de la dieta, el perfil metabólico y las adipocinas pro/antiinflamatorias. RESULTADOS: la terapia demostró ser efectiva para reducir el peso corporal (de 93,16 ± 16,96 a 88,36 ± 16,23; p = 0,0000001), el índice de masa corporal (de 34,01 ± 4,00 a 32,29 ± 3,96; p = 0,0000001) y la grasa corporal (de 38,25 ± 5,05 a 36,13 ± 5,00; p = 0,0000001). También hubo una mejora del perfil lipídico, incluidos el colesterol total (de 196,16 ± 34,78 a 183,53 ± 43,15; p = 0,001), el colesterol no HDL (de 142,00 ± 30,05 a 1333,69 ± 35,41; p = 0,01), el VLDL-colesterol (de 27,13 ± 12,4 a 22,06 ± 8,55; p = 0,002), y el metabolismo de la glucosa, incluyendo la glucosa (de 97,13 ± 10,43 a 92,6 ± 6,6; p = 0,004) y la insulina (de 13,05 ± 5,54 a 11,29 ± 4,85; p = 0,03). En cuanto a la ingesta de alimentos, hubo disminución en el consumo de calorías (de 1991,45 ± 677,78 a 1468,88 ± 390,56; p = 0,002), carbohidratos (de 50,37 ± 6,00 a 47,04 ± 8,67; p = 0,04), lípidos (de 31,83 ± 5,53 a 30,37 ± 7,04; p = 0,3) y carga glucémica (de 80,53 ± 39,88 a 54,79 ± 23,69; p = 0,02), y aumento del consumo de proteínas (de 18,3 ± 2,39 a 22,89 ± 4,90; p = 0,002). Se demostraron correlaciones positivas entre la concentración de insulina y la circunferencia de la cintura (r = 0,82; p = 0,003); la leptina, la grasa corporal y la circunferencia abdominal (r = 0,74; p = 0,01), y la fracción de colesterol LDL y el consumo total de colesterol (r = 0,69; p = 0,027). Se demostraron correlaciones negativas entre la leptina y el consumo de grasa monosaturada (r = -0,71; p = 0,02), y la adiponectina y la enzima hepática GGT (r = -0,65; p = 0,04). CONCLUSIONES: la terapia interdisciplinaria tuvo efectos positivos sobre el estado inflamatorio, mediado por la leptina, la adiponectina, y la calidad de la dieta. Nuestros hallazgos sugieren la efectividad y la relevancia clínica de la terapia clínica interdisciplinaria aplicada a la obesidad

Higher increase degree of FGF21 post long-term interdisciplinary weight loss therapy preserves the free fat mass and rest metabolic rate in adolescents with obesity.

Objective Fibroblast growth factor 21 (FGF21) is among the activators that can stimulate thermogenesis in the white adipose tissue and brown adipose tissue. People with obesity have elevated blood levels of FGF21, but also develop resistance to its action, impairing its beneficial role. Inversely, clinical treatments to weight loss has been pointed out as an important therapy for increasing and recovering sensitivity to FGF21. The aim was to analyse the effect of long-term weight loss interdisciplinary intervention on FGF21 and body composition. Subjects and methods Eighty-six post-pubertal obese adolescents (14-19 years-old), were submitted to 20 weeks of weight loss therapy (clinical, nutritional, psychological and physical exercise support). Anthropometric measures, body composition and rest metabolic rate (RMR) by bioelectrical impedance, and serum FGF21 sample by ELISA were evaluated. The adolescents were grouped according to FGF21 individual delta variations after therapy: Higher Increase (HI); lower increase (LI); lower decrease (LD); higher decrease (HD). Results All groups present weight loss. Only in FGF21 ≥ 76,5 pg/mL variation the free-fat-mass and rest metabolic rate were preserved and to others group these variables were significantly reduced. Conclusion High increase in FGF21 can contribute to preservation of FFM and RMR after weight loss therapy, could have important implications for energy balance regulation. Future studies are necessary to continue determining the role of magnitude effects of FGF21 levels in obesity to improve clinical practice, especially in paediatrics population.

High levels of adiponectin attenuate the detrimental association of adiposity with insulin resistance in adolescents.

BACKGROUND AND AIM: This study aimed to: i) examine the differences in insulin resistance (IR) across adiposity levels; and ii) ascertain whether high levels of adiponectin attenuate the detrimental association of adiposity with IR in adolescents. METHODS AND RESULTS: A total of 529 adolescents aged 12-18 years participated in this cross-sectional study (267 girls). Anthropometry and body adiposity parameters [body mass index (BMI), sum of skinfolds, body fat percentage (BF %) by bio-impedance analysis and waist circumference (WC)], were measured according to standardized procedures and categorized into age- and sex-specific quartiles. Socioeconomic status, pubertal stage and lifestyle determinants (Mediterranean diet adherence and cardiorespiratory fitness) were gathered and used as confounders. Serum adiponectin and IR (homeostasis model assessment of insulin resistance [HOMA-IR] estimated from fasting serum insulin and glucose were assessed. Analysis of covariance (ANCOVA) showed that HOMA-IR increased in a linear fashion throughout the quartiles of all adiposity measures (p < 0.001 for all), independently of age, sex, pubertal stage, socioeconomic status, adherence to the Mediterranean diet and cardiorespiratory fitness. Two-way ANCOVA showed that adolescents in the higher quartile of adiposity for BF%, BMI, WC and skinfolds sum (Q4) presented the highest adiponectin levels, and had 0.77 Standard Deviation (SD), 0.8 SD, 0.85 SD and 0.8 SD lower HOMA-IR, respectively (p < 0.01) than their low adiponectin group counterparts, after adjustments for potential confounders. CONCLUSION: Higher adiponectin levels may attenuate the detrimental association between adiposity and IR, particularly in subjects with higher adiposity.

Interdisciplinary therapy had positive effects on inflammatory state, mediated by leptin, adiponectin, and quality of diet in obese women.

INTRODUCTION: Background: obesity is a chronic disease associated with inadequate eating habits and reduced levels of physical activity. Because of obesity, the risk for comorbidities is increased, especially for cardiovascular diseases, insulin resistance, and increased pro-inflammatory factors. The aim of the present investigation was to analyze potential correlations between pro/anti-inflammatory adipokines, glycemic index, and other markers of diet quality using a metabolic profile in women undergoing interdisciplinary weight loss therapy. Methods: thirty-two women with obesity were enrolled in a 12-week program of interdisciplinary therapy combining a clinical, nutritional, and physical exercise approach. Body composition, quality of diet, metabolic profile, and pro/anti-inflammatory adipokines were analyzed. Results: the therapy showed to be effective in reducing body weight, body mass index, and body fat. There was also an improvement in lipid profile, including total cholesterol, non-HDL-cholesterol, VLDL-cholesterol, triglycerides and glucose metabolism, including glucose, and insulin. As for food intake, there was a decrease in calorie consumption, carbohydrates, lipids, and glycemic load, and an increased consumption of proteins. Positive correlations were demonstrated between insulin concentration and waist circumference; leptin and body fat and abdominal circumference; and LDL-cholesterol fraction and total cholesterol consumption. Negative correlations were demonstrated between leptin and monosaturated fat consumption; and adiponectin and liver enzyme GGT levels. Conclusions: interdisciplinary therapy had positive effects on inflammatory state, mediated by leptin, adiponectin, and quality of diet. Our findings suggest the effectiveness and clinical relevance of the interdisciplinary clinical therapy applied for obesity.

INTRODUCCIÓN: Introducción: la obesidad es una enfermedad crónica asociada con hábitos alimentarios inadecuados y niveles reducidos de actividad física. Debido a la obesidad, el riesgo de comorbilidad aumenta, especialmente el de las enfermedades cardiovasculares, la resistencia a la insulina y el aumento de los factores proinflamatorios. El objetivo investigación fue analizar las posibles correlaciones entre las adipocinas pro/antiinflamatorias, el índice glucémico y otros marcadores de calidad de la dieta con el perfil metabólico en mujeres sometidas a terapia interdisciplinaria para perder peso. Métodos: treinta y dos mujeres con obesidad participaron en 12 semanas de terapia interdisciplinaria en la que se combinaron los enfoques clínico, nutricional y de ejercicio físico. Se analizaron la composición corporal, la calidad de la dieta, el perfil metabólico y las adipocinas pro/antiinflamatorias. Resultados: la terapia demostró ser efectiva para reducir el peso corporal, el índice de masa corporal y la grasa corporal. También hubo una mejora del perfil lipídico, incluidos el colesterol total, el colesterol no HDL, el VLDL-colesterol , y el metabolismo de la glucosa, incluyendo la glucosa y la insulina. En cuanto a la ingesta de alimentos, hubo disminución en el consumo de calorías, carbohidratos, lípidos y carga glucémica, y aumento del consumo de proteínas. Se demostraron correlaciones positivas entre la concentración de insulina y la circunferencia de la cintura ; la leptina, la grasa corporal y la circunferencia abdominal, y la fracción de colesterol LDL y el consumo total de colesterol. Se demostraron correlaciones negativas entre la leptina y el consumo de grasa monosaturada, y la adiponectina y la enzima hepática GGT. Conclusiones: la terapia interdisciplinaria tuvo efectos positivos sobre el estado inflamatorio, mediado por la leptina, la adiponectina, y la calidad de la dieta. Nuestros hallazgos sugieren la efectividad y la relevancia clínica de la terapia clínica interdisciplinaria aplicada a la obesidad.

An Interdisciplinary Weight Loss Program Improves Body Composition and Metabolic Profile in Adolescents With Obesity: Associations With the Dietary Inflammatory Index.

Background and Aims: The prevalence of overweight and obesity consitutes a global epidemic and it is growing around the world. Food and nutrition are essential requirements for promoting health and protecting against non-communicable chronic diseases, such as obesity and cardiovascular disease. Specific dietary components may modulate inflammation and oxidative stress in obese individuals. The Dietary Inflammatory Index (DII®) was developed to characterize the anti- and pro-inflammatory effects of individuals' diet. Few studies have investigated the role of diet-associated inflammation in adolescents with obesity. The present study aims to investigate the effects of an interdisciplinary weight loss therapy on DII scores and cardiometabolic risk in obese adolescents and possibles correlations. Methods: A total of 45 volunteers (14-19 years old) were recruited and enrolled for long-term interdisciplinary therapy including clinical, nutritional, psychological counseling, and exercise training. Adolescents had access to videos about health education weekly. Body composition and inflammatory and serum profiles were evaluated at baseline and after intervention. The food intake was obtained by 24-h food recall. Data was used to calculate energy-adjusted DII (E-DII) scores. Negative scores indicate an anti-inflammatory diet and positive scores indicates a pro-inflammatory diet. The sample was divided according to whether individuals increased or decreased E-DII scores after therapy. Results: After therapy the body mass index (BMI), body weight, body fat, abdominal, waist, neck, and hip circumferences decreased significantly. The mean of high-density lipoprotein cholesterol (HDL-c) increased after the therapy. There was found an improvement of inflammatory and cardiometabolic parameters. In exploratory analyses, this occurred mainly when the EDII improved. Conclusion: Long-term interdisciplinary therapy combined with a health education website improved inflammatory serum markers in obese adolescents. Reduction in DII scores was associated with reduction of cardiometabolic parameters, suggesting that an anti-inflammatory diet may be an effective strategy to prevent and treat obesity and related comorbidities. Trial: http://www.ensaiosclinicos.gov.br/rg/RBR-6txv3v/, Register Number: RBR-6txv3v.

Homeostatic model assessment of adiponectin (HOMA-Adiponectin) as a surrogate measure of insulin resistance in adolescents: Comparison with the hyperglycaemic clamp and homeostatic model assessment of insulin resistance.

BACKGROUND: Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated. OBJECTIVES: To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance. METHODS: This was a cross-sectional study of 56 adolescents (aged 10-18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis. RESULTS: In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR. CONCLUSIONS: The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.

Effects of magnitude of visceral adipose tissue reduction: Impact on insulin resistance, hyperleptinemia and cardiometabolic risk in adolescents with obesity after long-term weight-loss therapy.

AIM: To investigate the association between visceral adipose tissue loss and insulin resistance and hyperleptinemia in adolescents with obesity submitted to interdisciplinary weight-loss therapy. METHODS: A total of 172 post-pubertal adolescents (body mass index greater than the 95th percentile of the Centers for Disease Control and Prevention reference growth charts) were recruited for the study. The adolescents were assigned to long-term weight-loss therapy. Body composition, visceral and subcutaneous fat, glucose metabolism, lipid profile, hepatic enzymes and leptin concentration were measured. After the therapy, the adolescents were allocated to three different groups according to the tertile of visceral fat reduction. RESULTS: Positive effects on body composition were observed in all analysed groups independent of visceral fat reduction. It was found that visceral fat was an independent predictor of insulin resistance in the investigated population. Obese adolescents who lost a higher proportion of visceral adipose tissue (>1.8 cm) demonstrated improved metabolic and inflammatory parameters twice as much than those who presented smaller losses. Positive correlations between visceral fat reduction and glucose metabolism, lipid profile, hepatic enzymes and homeostasis model assessment of insulin resistance index were demonstrated. CONCLUSION: The magnitude of the reduction in visceral fat was an independent predictor of insulin resistance, hyperleptinemia and metabolic disorders related to obese adolescents.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy.

OBJECTIVES: Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. SUBJECTS AND METHODS: Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). RESULTS: Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. CONCLUSIONS: It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy

ABSTRACT Objectives: Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. Subjects and methods: Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). Results: Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. Conclusions: It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

The Long-Term Impact of High Levels of Alpha-Melanocyte-Stimulating Hormone in Energy Balance Among Obese Adolescents.

BACKGROUND: Deregulation of orexigenic and anorexigenic pathways occurs among adolescents with obesity. Alpha-melanocyte-stimulating hormone (α-MSH) is a key catabolic mediator of energy homeostasis and an important anorexigenic neuropeptide in the control of energy balance and thermogenesis. However, it was not well explored if α-MSH can modulate long-term weight loss therapy responses in a dependent manner according to its concentration. Our hypothesis is that a high α-MSH concentration at baseline promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents. METHODS: One hundred ten post-pubertal obese adolescents (body mass index >95th percentile) were submitted to 1 year of interdisciplinary therapy (clinical, nutritional, psychological, physical exercise, and physiotherapy support). Body composition and plasma levels of α-MSH, neuropeptide Y (NPY), melanin-concentrating hormone, and agouti-related peptide (AgRP) were measured before and after therapy. The volunteers were grouped on the basis of Tertiles of α-MSH concentration: Low (<0.75 ng/mL), Medium (≤0.76 to ≥1.57 ng/mL), and High (>1.57 ng/mL). Significance was set as p < 0.05. RESULTS: The treatment promoted a significant improvement in body adiposity and fat free mass for all groups. It is important to note that only in the high α-MSH group, a significant increase of the α-MSH/NPY ratio and decrease NPY/AgRP ratio post treatment were observed. CONCLUSION: The high α-MSH concentration promotes better modulation of anorexigenic/orexigenic pathways in obese adolescents following long-term weight loss therapy and this is important in clinical practice.

Hypertriglyceridemic Waist Phenotype Indicates Insulin Resistance in Adolescents According to the Clamp Technique in the BRAMS Study.

OBJECTIVE: This study aimed to identify cutoff points for detecting hypertriglyceridemic waist phenotype (HTWP) in adolescents and to investigate the association of the HTWP with insulin resistance (IR) and metabolic syndrome components. METHODS: A multicentric cross-sectional study of 861 adolescents (10-19 years of age, 504 girls) was conducted. Pubertal stage, anthropometric, and laboratory parameters were assessed. IR was assessed by Homeostasis Model Assessment for Insulin Resistance (HOMA1-IR) index and hyperglycemic clamp (n = 80). HTWP was defined by the presence of increased plasma triglycerides (TGs) and increased waist circumference (WC) according to cutoff points obtained in ROC curve analysis given the HOMA1-IR index as a reference method. RESULTS: Cutoffs for WC and TGs, with a higher sum of sensitivity (S) and specificity (E), were, respectively: >84 cm (S:65.1%, E:71.9%) and >87 mg/dL (S:65.1%, E:73.4%) in pubertal girls; >88.5 cm (S:80.2%, E:60.2%) and >78 mg/dL (S:60.5%, E:53.2%) in postpubertal girls; >94 cm (S:73.1%, E:83.1%) and >79 mg/dL (S:61.5%, E:60.2%) in pubertal boys; and >99 cm (S:81.3%, E:78.7%) and >86 mg/dL in postpubertal boys (S:68.1%, E:60.7%). HTWP frequency was 27.5%. In the phenotype presence, after adjustment for age and pubertal stage, blood pressure and fasting glucose levels were elevated and high-density lipoprotein cholesterol was lower (p < 0.001). Adolescents with the HTWP showed more IR, evaluated both by the HOMA1-IR and by the clamp test (p < 0.003). CONCLUSION: The findings suggest HTWP as an IR status in adolescents. Cutoff point standardization for gender and pubertal stage, combined with the ease of application of the method, may allow their use for screening adolescents who would most benefit from lifestyle changes.