Exercise training induces alteration of clock genes and myokines expression in tumor-bearing mice.

To investigate the impact of different exercise training schedules (following a fixed schedule or at random times of the day) on clock genes and myokine expression patterns in the skeletal muscle of tumor-bearing mice. Mice were divided into three groups: tumor (LLC), tumor + exercise training (LLC + T) always performed at the same time of the day (ZT2) and exercise training at random times of the day (ZTAlt). Mice were inoculated subcutaneously with Lewis lung carcinoma cells. The gastrocnemius muscle was dissected and the clock gene expression (Clock/Per1/Per2/Per3/Rev-Erbα/GAPDH) was investigated by quantitative reverse transcription polymerase chain reaction with SYBR® Green. Myokine content in muscle (tumour necrosis factor alpha/IL-10/IL-4) was assessed by enzyme-linked immunosorbent assay. At the end of the protocol, the trained groups showed a reduction in total weight, when compared to Lewis lung carcinoma. Tumor weight was lower in the LLC + T (ZTAlt), when compared to LLC. Clock gene mRNA expression showed a significant increase for ZT20 in the groups that performed physical exercise at LLC + T (ZTAlt), when compared with LLC. The Per family showed increased mRNA expression in ZT4 in both trained mice groups, when compared with LLC. LLC + T (ZTAlt) presented reduction of the expression of anti-inflammatory myokines (Il-10/IL-4) during the night, compared with LLC + T(ZT2). Exercise training is able to induce marked modification of clock gene expression and of the production of myokines, in a way that is dependent on schedule exercise training strategy. Taken together, the results show that exercise is a potent Zeitgeber and may thus contribute to change clock genes expression and myokines that are able to reduce the tumor weight.

Formoterol reduces muscle wasting in mice undergoing doxorubicin chemotherapy.

Background: Even though doxorubicin (DOX) chemotherapy promotes intense muscle wasting, this drug is still widely used in clinical practice due to its remarkable efficiency in managing cancer. On the other hand, intense muscle loss during the oncological treatment is considered a bad prognosis for the disease's evolution and the patient's quality of life. In this sense, strategies that can counteract the muscle wasting induced by DOX are essential. In this study, we evaluated the effectiveness of formoterol (FOR), a ß2-adrenoceptor agonist, in managing muscle wasting caused by DOX. Methods and results: To evaluate the effect of FOR on DOX-induced muscle wasting, mice were treated with DOX (2.5 mg/kg b.w., i.p. administration, twice a week), associated or not to FOR treatment (1 mg/kg b.w., s.c. administration, daily). Control mice received vehicle solution. A combination of FOR treatment with DOX protected against the loss of body weight (p<0.05), muscle mass (p<0.001), and grip force (p<0.001) promoted by chemotherapy. FOR also attenuated muscle wasting (p<0.01) in tumor-bearing mice on chemotherapy. The potential mechanism by which FOR prevented further DOX-induced muscle wasting occurred by regulating Akt/FoxO3a signaling and gene expression of atrogenes in skeletal muscle. Conclusions: Collectively, our results suggest that FOR can be used as a pharmacological strategy for managing muscle wasting induced by DOX. This study provides new insights into the potential therapeutic use of FOR to improve the overall wellbeing of cancer patients undergoing DOX chemotherapy.

Aerobic training improves NAFLD markers and insulin resistance through AMPK-PPAR-α signaling in obese mice.

Liver steatosis is one of the main drivers for the development of whole-body insulin resistance. Conversely, aerobic training (AT) has been suggested as non-pharmacological tool to improve liver steatosis, however, the underlying molecular mechanism remains unclear. Therefore, the aim of this study was to analyze the effect of 8-weeks AT in non-alcoholic liver disease (NAFLD) outcomes in obese mice. Male C57BL/6 J wild type (WT) were fed with standard (SD) or high-fat diet (HFD) for 12-weeks. Another group fed with HFD underwent 8-weeks of AT (60% of maximum velocity), initiated at the 5th week of experimental protocol. We measured metabolic, body composition parameters, protein and gene expression inflammatory and metabolic mediators. We found that AT attenuates the weight gain, but not body fat accumulation. AT improved triacylglycerol and non-esterified fatty acid plasma concentrations, and also whole-body insulin resistance. Regarding NAFLD, AT decreased the progression of macrovesicular steatosis and inflammation through the upregulation of AMPK Thr172 phosphorylation and PPAR-α protein expression. Moreover, although no effects of intervention in PPAR-γ protein concentration were observed, we found increased levels of its target genes Cd36 and Scd1 in exercised group, demonstrating augmented transcriptional activity. AT reduced liver cytokines concentrations, such as TNF-α, IL-10, MCP-1 and IL-6, regardless of increased Ser536 NF-κB phosphorylation. In fact, none of the interventions regulated NF-κB target genes Il1b and Cccl2, demonstrating its low transcriptional activity. Therefore, we conclude that AT attenuates the progression of liver macrovesicular steatosis and inflammation through AMPK-PPAR-α signaling and PPAR-γ activation, respectively, improving insulin resistance in obese mice.

Endurance Exercise Mitigates Immunometabolic Adipose Tissue Disturbances in Cancer and Obesity.

Adipose tissue is considered an endocrine organ whose complex biology can be explained by the diversity of cell types that compose this tissue. The immune cells found in the stromal portion of adipose tissue play an important role on the modulation of inflammation by adipocytokines secretion. The interactions between metabolic active tissues and immune cells, called immunometabolism, is an important field for discovering new pathways and approaches to treat immunometabolic diseases, such as obesity and cancer. Moreover, physical exercise is widely known as a tool for prevention and adjuvant treatment on metabolic diseases. More specifically, aerobic exercise training is able to increase the energy expenditure, reduce the nutrition overload and modify the profile of adipocytokines and myokines with paracrine and endocrine effects. Therefore, our aim in this review was to cover the effects of aerobic exercise training on the immunometabolism of adipose tissue in obesity and cancer, focusing on the exercise-related modification on adipose tissue or immune cells isolated as well as their interaction.

Exercise Reduces the Resumption of Tumor Growth and Proteolytic Pathways in the Skeletal Muscle of Mice Following Chemotherapy.

The pathogenesis of muscle atrophy plays a central role in cancer cachexia, and chemotherapy contributes to this condition. Therefore, the present study aimed to evaluate the effects of endurance exercise on time-dependent muscle atrophy caused by doxorubicin. For this, C57 BL/6 mice were subcutaneously inoculated with Lewis lung carcinoma cells (LLC group). One week after the tumor establishment, a group of these animals initiated the doxorubicin chemotherapy alone (LLC + DOX group) or combined with endurance exercise (LLC + DOX + EXER group). One group of animals was euthanized after the chemotherapy cycle, whereas the remaining animals were euthanized one week after the last administration of doxorubicin. The practice of exercise combined with chemotherapy showed beneficial effects such as a decrease in tumor growth rate after chemotherapy interruption and amelioration of premature death due to doxorubicin toxicity. Moreover, the protein degradation levels in mice undergoing exercise returned to basal levels after chemotherapy; in contrast, the mice treated with doxorubicin alone experienced an increase in the mRNA expression levels of the proteolytic pathways in gastrocnemius muscle (Trim63, Fbxo32, Myostatin, FoxO). Collectively, our results suggest that endurance exercise could be utilized during and after chemotherapy for mitigating muscle atrophy promoted by doxorubicin and avoid the resumption of tumor growth.

Palmitoleic acid reduces high fat diet-induced liver inflammation by promoting PPAR-γ-independent M2a polarization of myeloid cells.

Palmitoleic acid (POA, 16:1n-7) is a lipokine that has potential nutraceutical use to treat non-alcoholic fatty liver disease. We tested the effects of POA supplementation (daily oral gavage, 300 mg/Kg, 15 days) on murine liver inflammation induced by a high fat diet (HFD, 59% fat, 12 weeks). In HFD-fed mice, POA supplementation reduced serum insulin and improved insulin tolerance compared with oleic acid (OA, 300 mg/Kg). The livers of POA-treated mice exhibited less steatosis and inflammation than those of OA-treated mice with lower inflammatory cytokine levels and reduced toll-like receptor 4 protein content. The anti-inflammatory effects of POA in the liver were accompanied by a reduction in liver macrophages (LM, CD11c+; F4/80+; CD86+), an effect that could be triggered by peroxisome proliferator activated receptor (PPAR)-γ, a lipogenic transcription factor upregulated in livers of POA-treated mice. We also used HFD-fed mice with selective deletion of PPAR-γ in myeloid cells (PPAR-γ KOLyzCre+) to test whether the beneficial anti-inflammatory effects of POA are dependent on macrophages PPAR-γ. POA-mediated improvement of insulin tolerance was tightly dependent on myeloid PPAR-γ, while POA anti-inflammatory actions including the reduction in liver inflammatory cytokines were preserved in mice bearing myeloid cells deficient in PPAR-γ. This overlapped with increased CD206+ (M2a) cells and downregulation of CD86+ and CD11c+ liver macrophages. Moreover, POA supplementation increased hepatic AMPK activity and decreased expression of the fatty acid binding scavenger receptor, CD36. We conclude that POA controls liver inflammation triggered by fat accumulation through induction of M2a macrophages independently of myeloid cell PPAR-γ.

Moderate aerobic exercise-induced cytokines changes are disturbed in PPARα knockout mice.

The nuclear transcriptional factor peroxisome proliferator activated receptor alpha (PPARα) plays a role in regulating genes involved in lipid metabolism, adipogenesis and inflammation. We aimed to assess the role of PPARα on exercise-mediated locally produced cytokines in adipose fat deposits and skeletal muscle. C57BL/6 (WT) and PPARα knockout (PPARα-/-) mice were examined. Each genotype was randomly subdivided into three groups: non-exercised, and euthanized 2 or 24 h after a moderate aerobic exercise session (run on a treadmill at 60% of maximum speed for 1 h). Fat content in gastrocnemius muscle and lipolytic activity in isolated adipose tissue from mesenteric (MEAT) and retroperitoneal (RPAT) adipose tissue were evaluated. In addition, Interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) content were evaluated by ELISA. WT mice showed a maximum lipolysis rate, as well as higher IL-6, IL-10, and IL10/TNF-α ratio values 2 h post-exercise (RPAT only) compared with PPARα-/- mice. Taken together, our data suggests that PPARα knockout mice exhibited reduced lipolysis and anti-inflammatory response in adipose tissue following exercise, PPARα appears to play an important role in immunomodulatory and lipolysis signaling after acute moderate exercise.

Macrophage immunophenotype but not anti-inflammatory profile is modulated by peroxisome proliferator-activated receptor gamma (PPARγ) in exercised obese mice.

Moderate aerobic training may be therapeutic for chronic low-grade inflammatory diseases due to the associated anti-inflammatory response that is mediated by immune cells. The peroxisome proliferator-activated receptor gamma (PPARγ) regulates the M1 (pro-inflammatory) and M2 (anti-inflammatory) polarization, as well as the immunometabolic response of macrophages. Against this background, the present study seeks to clarify whether the conditional deletion of PPARγ in macrophages would have any effect on the anti-inflammatory role of moderate aerobic training. To test this hypothesis, two mice strains were used: PPARγ LyzCre+/+ (KO) and littermates control animals (WT). Each genotype was divided into 1) sedentary high-fat diet (HF) and 2) high-fat diet and moderate aerobic training (HFT) (n = 5-8 per group). The experimental protocol lasted for 12 weeks, comprising 4 weeks of HF diet only and 8 weeks of HF diet and aerobic training (5 times/week, 50-60 minutes/day at 60% of maximum speed). Metabolic analyses were carried out on the serum glucose homeostase, adipose tissue morphology and cytokine content, and macrophage cytokine production.Immunophenotyping and gene expression were also performed. KO male mice were more prone to hypertrophy in the subcutaneous adipose tissue, though only the IL-1ß (p = 0.0049) was higher compared to the values observed in WT animals. Peritoneal macrophages from KO animals exhibited a marked inflammatory environment with an increase in TNF-α (p = 0.0008), IL- 1ß (p = 0.0017), and IL-6 (p < 0.0001) after lipopolysaccharide stimulation. The moderate aerobic training protected both genotypes from weight gain and reduced the caloric intake in the KO animals. Despite the attenuation of the M2 marker CD206 (p < 0.001) in the absence of PPAR-γ, the aerobic training modulated cytokine production in LPS stimulated peritoneal macrophages from both genotypes, reducing proinflammatory cytokines such as TNF-α (p = 0.0002) and IL-6 (p < 0.0001). Overall, our findings demonstrate the essential role of PPARγ in macrophage immunophenotypes. However, the deletion of PPARγ did not inhibit the exercise-mediated anti-inflammatory effect, underscoring the important role of exercise in modulating inflammation.

Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors γ deletion in macrophages.

BACKGROUND: Exercise is a powerful tool for prevention and treatment of many conditions related to the cardiovascular system and also chronic low-grade inflammation. Peroxisome proliferator-activated receptors γ (PPARγ) exerts an import role on the regulation of metabolic profile and subsequent inflammatory response, especially in macrophages. PURPOSE: To investigate the effects of 8-week moderate-exercise training on metabolic and inflammatory parameters in mice with PPARγ deficiency in myeloid cells. METHODS: Twelve-week old mice bearing PPARγ deletion exclusively in myeloid cells (PPARγlox/lox Lys Cre -/+ , knockout [KO]) and littermate controls (PPARγlox/lox Lys Cre -/- , wild type [WT]) were submitted to 8-week exercise training (treadmill running at moderate intensity, 5 days/week). Animals were evaluated for food intake, glucose homeostasis, serum metabolites, adipose tissue and peritoneal macrophage inflammation, and basal and stimulated cytokine secretion. RESULTS: Exercise protocol did not improve glucose metabolism or adiponectin concentrations in serum of KO mice. Moreover, the absence of PPARγ in macrophages exacerbated the proinflammatory profile in sedentary mice. Peritoneal cultured cells had higher tumor necrosis factor-α (TNF-α) secretion in nonstimulated and lipopolysaccharide (LPS)-stimulated conditions and higher Toll-4 receptor (TLR4) gene expression under LPS stimulus. Trained mice showed reduced TNF-α content in adipose tissue independently of the genotype. M2 polarization ability was impaired in KO peritoneal macrophages after exercise training, while adipose tissue-associated macrophages did not present any effect by PPARγ ablation. CONCLUSION: Overall, PPARγ seems necessary to maintain macrophages appropriate response to inflammatory stimulus and macrophage polarization, affecting also whole body lipid metabolism and adiponectin profile. Exercise training showed as an efficient mechanism to restore the immune response impaired by PPARγ deletion in macrophages.

High Blood Pressure Combined with Sedentary Behavior in Young People: A Systematic Review.

BACKGROUND: High blood pressure (HBP) is a cardiovascular risk factor that can initiate in childhood and adolescence and may be associated with other risk factors such as sedentary lifestyles. Therefore, verifying if these associations occur from the earliest ages is of fundamental importance. OBJECTIVES: to report the prevalence of HBP combined with sedentary behavior through a systematic review. DESIGN AND METHODS: The research was performed based on studies published between 2010 and 2016 in Medline, Web of Science, Excerpta Medica (EMBASE), and Scielo, using terms related to: 'sedentary behavior' OR 'screen time' AND 'high blood pressure'. In the initial search, 821 studies were found and after exclusions twelve studies were included in the review. RESULTS: Twelve studies addressing the relationship between sedentary behavior and HBP were found. Eighty-three percent of the studies evaluated sedentary behavior using a questionnaire (n = 10). The majority of studies analyzed in the review were conducted in North America (41.6%). Only four studies presented the prevalence of HBP related to sedentary behavior (variation 1-22.9%). In seven studies a close relationship between sedentary behavior and HBP was observed. CONCLUSIONS: Although most studies observed a relationship between sedentary behavior and HBP, the results still need to be further explained. Based on the findings of this review, follow-up studies and objective measurements of time spent in sedentary behavior in young people could help to determine the cause-effect relationship between sedentary behavior and HBP in pediatric populations.

Macrophage Polarization: Implications on Metabolic Diseases and the Role of Exercise.

Macrophages are cells of the innate immune response that trigger inflammation resolution. The phenotype of "classically activated macrophages" (M1) has anti-tumoricidal and anti-bactericidal activities. On the other hand, "alternatively activated macrophages" (M2) are involved in tissue remodeling and immunomodulatory functions. The change in the polarization of macrophages varies according to the diversity of cytokines present in the microenvironment or by the stimuli of an antigen. It involves such factors as interferon-regulatory factors, peroxisome proliferator-activated receptors (PPARs), hypoxia-inducible factors (HIFs), and signal transducers and activators of transcription (STATs). Switching the phenotype of macrophages can help attenuate the development of an inflammatory disease. Exercise can promote alterations in the number of innate immune cells and stimulates phagocytic function. Chronic exercise seems to inhibit macrophage infiltration into adipose tissue by attenuating the expression of F4/80 mRNA. Furthermore, exercise may also increase the expression of M2 markers and reduce TNF-α and TLR4 mRNA expression, which activates the inflammatory pathway of NF-κB. Chronic exercise reduces ß2-adrenergic receptors in monocytes and macrophages by modulating TLR4 signaling as well as suppressing IL-12 production, a stimulator of interferon Y. In this review, we discuss macrophage polarization in metabolic diseases and how exercise can modulate macrophage plasticity.

Effect of concurrent training on gender-specific biochemical variables and adiposity in obese adolescents.

OBJECTIVE: The purpose of the present study was to analyze the effects of a 20-week concurrent training (20 WCT) intervention program on gender-specific body composition and metabolic variables in obese adolescents. SUBJECTS AND METHODS: Sample was composed of twenty-five obese adolescents, aged between 12 and 15 (13.4 ± 0.96) years. Fat-free mass (FFM), percentage trunk fat mass (TFM%) and percentage fat mass (%FM) were evaluated through dual-energy X-ray absorptiometry (DXA). Measurement of intra-abdominal adiposity (IAAT) was performed using ultrasound. Blood pressure was measured and blood samples analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and plasma glucose. All participants performed the concurrent training (combination of weight training and aerobic training) three times per week, one hour per day, for 20 weeks. Descriptive analysis and analysis of variance (ANOVA) for repeated measures were used to compare baseline, 10 week and 20 week moments using the Bonferroni post-hoc test. Statistical significance was set at p < 0.05. Significant decrease in TC, LDL-c and TFM% were verified in both genders after the 10 initial weeks of concurrent training. RESULTS: A significant increase in height was found in both the male and female groups (p = 0.001 and p = 0.047, respectively), after 20 weeks of concurrent training. In addition, several modifications were observed in body composition and metabolic variables, with a significant decrease in BMI (p = 0.002 and p = 0.017), BMI z-score (p = 0.033 and p = 0.004), FM% (p = 0.002 and p = 0.002), TFM% (p = 0.009 and p = 0.018), TC (p = 0.042 and p = 0.001) and LDL-c (p = 0.006 and p = 0.001) in the male and female groups, respectively, after 20 weeks of intervention when compared with baseline. CONCLUSION: Our results identified that concurrent training was an effective intervention for treating metabolic variable and body composition disorders, in both genders, by decreasing adiposity with consequent improvement in BMI and BMI z-scores, and enhancement in lipid profile variables.

Macronutrient intake is correlated with dyslipidemia and low-grade inflammation in childhood obesity but mostly in male obese / La ingesta de macronutrientes se correlaciona con la dislipidemia y la inflamación de bajo grado en la obesidad infantil, pero sobre todo en los hombres obesos

Background & Aims: condition of hypoxia caused by hypertrophy of adipose cells in obesity triggers macrophages recruitment and production of cytokines. Additionally, high consumption of saturated fatty acids (SFA) and high glycemic index meals may contribute to oxidative stress and chronic low-grade inflammation by increases NF-kB activation. Thus, the aim of the study was to analyze the contribution of the macronutrients intake in the metabolic and inflammatory profile, by levels of lipoproteins, insulin resistance, anti and pro inflammatory cytokines, in obese adolescents according the gender. Methods: sample was composed by 37 adolescents, both genders, identified as obese by body mass index (BMI). Body composition was assessed by Dual-energy X-ray absorptiometry (DEXA) and measures of intra-abdominal adiposity (IAAT) and subcutaneous adiposity tissue (SAT) were done by ultrasound. Biochemical analyses were done and the measurement of cytokines; fatty acids and insulin were performed by the technique of immunoassay ELISA. The estimation of macronutrients consumption was made by 3 day food register regarding food intake. Statistical significance was set at p-value < 5% and the statistical software SPSS version 17.0 (SPSS Inc, Chicago, IL) performed all analyses. Results: BMI (p = 0.316), FM (p = 0.416), IAAT (p = 0.505) and SAT (p = 0.935) presented similarities between genders. Cytokines and metabolic variables values were similar between the groups. Only in the male group, metabolic variables and cytokines were significant correlated with the consumption of total lipids or its fractions. Was observed that insulin concentration had significant interaction with MUFA(g) (β = -18.4; p = 0.004) and adiponectin with CHO(g) (β = -58.2; p = 0.032) in the group male and female, respectively. Conclusions: macronutrients intake is associated with low-grade inflammation in obesity, by production of inflammatory cytokines and alteration of the lipid profile, especially male obese adolescents which seem to be more responsive of this consumption when compared with female obese adolescents (AU)

Introducción y objetivo: la hipoxia causada por la hipertrofia de las células adiposas en la obesidad desencadena macrófagos de reclutamiento y la producción de citoquinas. Además, el alto consumo de ácidos grasos saturados (AGS) y las comidas con alto índice glucémico pueden contribuir al estrés oxidativo y la inflamación crónica de bajo grado por los aumentos de activación de NF-kB. Por lo tanto, el objetivo del estudio fue analizar la contribución de la ingesta de macronutrientes en el perfil metabólico e inflamatorio, por niveles de lipoproteínas, resistencia a la insulina, citoquinas anti y pro inflamatorias, en adolescentes obesos según el género. Métodos: la muestra estaba compuesta por 37 adolescentes, de ambos géneros, identificados como obesos según el índice de masa corporal (IMC). La composición corporal se evaluó mediante absorciometría de energía dual de rayos X (DEXA) y medidas de adiposidad intraabdominal (IAAT) y del tejido adiposo subcutáneo (SAT) se realizaron mediante ecografía. Los análisis bioquímicos se realizaron mediante la medición de citoquinas; los ácidos grasos y la insulina se realizaron por la técnica de ELISA. La estimación del consumo de macronutrientes fue llevado a cabo durante tres días mediante el registro de alimentos con respecto a la ingesta total. La significación estadística se estableció en el valor p < 5% y todos los análisis se realizaron con el programa estadístico SPSS Inc, Chicago, IL, versión 17.0. Resultados: IMC (p = 0,316), FM (p = 0,416), IAAT (p = 0,505) y SAT (p = 0,935) presentan similitudes entre géneros. Los valores de citoquinas y de variables metabólicas fueron similares entre los grupos. Solo en el grupo masculino, variables metabólicas y citoquinas fueron correlacionadas con el consumo de lípidos totales o sus fracciones. Se observó que la concentración de insulina tenía interacción significativa con MUFA (g) (β = -18,4; p = 0,004) y la adiponectina con CHO (g) (β = -58,2; p = 0,032) en el grupo masculino y femenino, respectivamente. Conclusiones: la ingesta de macronutrientes se asocia con la inflamación de bajo grado en la obesidad, por la producción de citoquinas inflamatorias y la alteración del perfil lipídico, en los adolescentes obesos, especialmente masculinos, que parecen ser más sensibles a este consumo en comparación con las adolescentes obesas femeninas (AU)

MACRONUTRIENT INTAKE IS CORRELATED WITH DYSLIPIDEMIA AND LOW-GRADE INFLAMMATION IN CHILDHOOD OBESITY BUT MOSTLY IN MALE OBESE.

BACKGROUND & AIMS: condition of hypoxia caused by hypertrophy of adipose cells in obesity triggers macrophages recruitment and production of cytokines. Additionally, high consumption of saturated fatty acids (SFA) and high glycemic index meals may contribute to oxidative stress and chronic low-grade inflammation by increases NF-kB activation. Thus, the aim of the study was to analyze the contribution of the macronutrients intake in the metabolic and inflammatory profile, by levels of lipoproteins, insulin resistance, anti and pro inflammatory cytokines, in obese adolescents according the gender. METHODS: sample was composed by 37 adolescents, both genders, identified as obese by body mass index (BMI). Body composition was assessed by Dual-energy X-ray absorptiometry (DEXA) and measures of intra-abdominal adiposity (IAAT) and subcutaneous adiposity tissue (SAT) were done by ultrasound. Biochemical analyses were done and the measurement of cytokines; fatty acids and insulin were performed by the technique of immunoassay ELISA. The estimation of macronutrients consumption was made by 3 day food register regarding food intake. Statistical significance was set at p-value < 5% and the statistical software SPSS version 17.0 (SPSS Inc, Chicago, IL) performed all analyses. RESULTS: BMI (p = 0.316), FM (p = 0.416), IAAT (p = 0.505) and SAT (p = 0.935) presented similarities between genders. Cytokines and metabolic variables values were similar between the groups. Only in the male group, metabolic variables and cytokines were significant correlated with the consumption of total lipids or its fractions. Was observed that insulin concentration had significant interaction with MUFA(g) (= -18.4; p = 0.004) and adiponectin with CHO(g) (= -58.2; p = 0.032) in the group male and female, respectively. CONCLUSIONS: macronutrients intake is associated with low-grade inflammation in obesity, by production of inflammatory cytokines and alteration of the lipid profile, especially male obese adolescents which seem to be more responsive of this consumption when compared with female obese adolescents.

Introducción y objetivo: la hipoxia causada por la hipertrofia de las células adiposas en la obesidad desencadena macrófagos de reclutamiento y la producción de citoquinas. Además, el alto consumo de ácidos grasos saturados (AGS) y las comidas con alto índice glucémico pueden contribuir al estrés oxidativo y la inflamación crónica de bajo grado por los aumentos de activación de NF-kB. Por lo tanto, el objetivo del estudio fue analizar la contribución de la ingesta de macronutrientes en el perfil metabólico e inflamatorio, por niveles de lipoproteínas, resistencia a la insulina, citoquinas anti y pro inflamatorias, en adolescentes obesos según el género. Métodos: la muestra estaba compuesta por 37 adolescentes, de ambos géneros, identificados como obesos según el índice de masa corporal (IMC). La composición corporal se evaluó mediante absorciometría de energía dual de rayos X (DEXA) y medidas de adiposidad intraabdominal (IAAT) y del tejido adiposo subcutáneo (SAT) se realizaron mediante ecografía. Los análisis bioquímicos se realizaron mediante la medición de citoquinas; los ácidos grasos y la insulina se realizaron por la técnica de ELISA. La estimación del consumo de macronutrientes fue llevado a cabo durante tres días mediante el registro de alimentos con respecto a la ingesta total. La significación estadística se estableció en el valor p.

Effect of concurrent training on gender-specific biochemical variables and adiposity in obese adolescents

Objective The purpose of the present study was to analyze the effects of a 20-week concurrent training (20 WCT) intervention program on gender-specific body composition and metabolic variables in obese adolescents.Subjects and methods Sample was composed of twenty-five obese adolescents, aged between 12 and 15 (13.4 ± 0.96) years. Fat-free mass (FFM), percentage trunk fat mass (TFM%) and percentage fat mass (%FM) were evaluated through dual-energy X-ray absorptiometry (DXA). Measurement of intra-abdominal adiposity (IAAT) was performed using ultrasound. Blood pressure was measured and blood samples analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and plasma glucose. All participants performed the concurrent training (combination of weight training and aerobic training) three times per week, one hour per day, for 20 weeks. Descriptive analysis and analysis of variance (ANOVA) for repeated measures were used to compare baseline, 10 week and 20 week moments using the Bonferroni post-hoc test. Statistical significance was set at p < 0.05. Significant decrease in TC, LDL-c and TFM% were verified in both genders after the 10 initial weeks of concurrent training.Results A significant increase in height was found in both the male and female groups (p = 0.001 and p = 0.047, respectively), after 20 weeks of concurrent training. In addition, several modifications were observed in body composition and metabolic variables, with a significant decrease in BMI (p = 0.002 and p = 0.017), BMI z-score (p = 0.033 and p = 0.004), FM% (p = 0.002 and p = 0.002), TFM% (p = 0.009 and p = 0.018), TC (p = 0.042 and p = 0.001) and LDL-c (p = 0.006 and p = 0.001) in the male and female groups, respectively, after 20 weeks of intervention when compared with baseline.Conclusion Our results identified that concurrent training was an effective intervention for treating metabolic variable and body composition disorders, in both genders, by decreasing adiposity with consequent improvement in BMI and BMI z-scores, and enhancement in lipid profile variables.

Treinamento concorrente e o treinamento funcional promovem alterações benéficas na composição corporal e esteatose hepática não alcoólica de jovens obesos / Concurrent training and functional training promotes beneficial changes in body composition and nonalcoholic fatty liver of obese youth

Comparar efeito do treinamento concorrente e o treinamento funcional na composição corporal, perfil lipídico e esteatose hepática não alcoólica (EHNA) em adolescentes obesos. Estudo longitudinal/analítico por amostragem não aleatória. Amostra de 49 adolescentes obesos (treinamento concorrenteENT#091;n=36ENT#093;; treinamento funcionalENT#091;n=13ENT#093;). Nos dois tipos de treinamento físico 50% de atividade aeróbia, e 50% resistida (concorrente: musculação; funcional: peso do próprio corpo e/ou pesos livres). Para distribuição normal aplicou-se Teste t de Student para dados pareados. Treinamento concorrente apresentou redução para lipoproteína de baixa densidade (-16,45%), colesterol total (-11,55%), gordura corporal (-8,52%) e gordura de tronco (-9,95%) e aumento da massa muscular (5,05%). Treinamento funcional reduziu 76,9% a ocorrência da EHNA, gordura corporal (-4,97%), gordura intra-abdominal (-19,90%), e aumento na massa muscular (4,18%). Devido ao alto acometimento da EHNA neste grupo, futuras investigações se fazem necessárias. Para tanto, o treinamento concorrente parece ser uma ferramenta útil para o tratamento da EHNA em adolescentes obesos.

To compare the effect of concurrent and functional exercise training on body composition, lipid profile and non-alcoholic steatohepatitis in obese adolescents. Longitudinal/analytical study by non-random sampling carried out with 49 obese adolescents (n=36 in concurrent and n=13 in functional exercise training). Both protocols had 50% of the session designed to aerobic activities and the other half session to resistance and functional training (activities using self-body weight and dumbbells). Set data had normal distribution and the paired sample t test was applied. Concurrent exercise training decreased low density lipoprotein (-16.45%), total cholesterol (-11.55%), body fatness (-8.52%), trunk fatness (-9.95%) and increased fat free mass (5.05%). On the other hand, functional exercise training decrease body fatness (-4.97%), trunk fatness (-5.11%), intra-abdominal adiposity (-19,9%), increase fat free mass (4.18%) and occurrence of non-alcoholic steatohepatitis (reduction of 76.9%). Concurrent training seems a relevant tool to the treatment of non-alcoholic steatohepatitis in obese adolescents.

Body composition variables as predictors of NAFLD by ultrasound in obese children and adolescents.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a disorder associated with excessive fat accumulation, mainly in the intra-abdominal region. A simple technique to estimate abdominal fat in this region could be useful to assess the presence of NAFLD, in obese subjects who are more vulnerable to this disease. The aim of this cross-sectional study was to verify the reliability of waist circumference and body composition variables to identify the occurrence of NAFLD in obese children and adolescents. METHODS: Sample was composed of 145 subjects, aged 11 to 17 years. Assessments of waist circumference (WC), trunk fat mass (TFM) and fat mass (FM) by dual-energy X-ray absorptiometry (DXA) and ultrasound for diagnosis of NAFLD and intra-abdominal adipose tissue (IAAT) were used. Correlation between variables was made by Spearman's coefficients; ROC curve parameters (sensitivity, specificity, area under curve) were used to assess the reliability of body composition variables to assess the presence of NAFLD. Statistical significance was set at 5%. RESULTS: Significant correlations were observed between NAFLD and WC (p = 0.001), TFM (p = 0.002) and IAAT (p = 0.001). The higher values of area under the ROC curve were for WC (AUC = 0.720), TFM (AUC = 0.661) and IAAT (AUC = 0.741). CONCLUSIONS: Our findings indicated that TFM, IAAT and WC present high potential to identify NAFLD in obese children and adolescents.

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents.

OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of body composition, lipid profile, and fatty liver diagnosis in obese adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an upper abdominal ultrasound was performed in order to diagnose fatty liver. The participants underwent concurrent training (association of weight training with aerobic training) three times per week, lasting one hour for 20 weeks. Statistical analysis included paired Student's(tm)s t-test and frequency analysis in order to verify the relative and absolute reductions of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body composition, with a decrease of total body fat percentage, total fat mass, trunk fat, and an a increase in the lean body mass. They also presented reduced size of liver lobes, decrease in total cholesterol and in LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements in body fat composition and lipid profile variables, besides reducing fatty liver prevalence rate.

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents / Efecto del entrenamiento concurrente sobre factores de riesgo y esteatosis hepatica en adolescentes obesos / Efeito do treinamento concorrente sobre fatores de risco e esteatose hepatica em adolescentes obesos

OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of body composition, lipid profile, and fatty liver diagnosis in obese adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an upper abdominal ultrasound was performed in order to diagnose fatty liver. The participants underwent concurrent training (association of weight training with aerobic training) three times per week, lasting one hour for 20 weeks. Statistical analysis included paired Studentâ€(tm)s t-test and frequency analysis in order to verify the relative and absolute reductions of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body composition, with a decrease of total body fat percentage, total fat mass, trunk fat, and an a increase in the lean body mass. They also presented reduced size of liver lobes, decrease in total cholesterol and in LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements in body fat composition and lipid profile variables, besides reducing fatty liver prevalence rate. .

OBJETIVO Analizar los efectos de 20 semanas de entrenamiento concurrente sobre las variables de composición corporal, perfil lipídico y diagnóstico de la esteatosis hepática en adolescentes obesos. MÉTODOS Se realizó un ensayo clínico abierto con 34 adolescentes obesos con edades entre los 12 y los 15 años (13,7±1,17). Se analizaron grasa corporal total y de tronco, colesterol total y sus fracciones (HDL, LDL y VLDL) y triglicéridos, siendo realizado examen de ultrasonografía abdominal superior para diagnosticar esteatosis hepática. Los participantes fueron sometidos al entrenamiento concurrente (asociación de entrenamiento con pesos y ejercicio aeróbico) tres veces por semana, con duración de una hora clase durante 20 semanas. Para el tratamiento estadístico, se realizaron análisis descriptivo, prueba t de Student pareada y análisis de frecuencia, a fin de verificar las reducciones relativa y absoluta del diagnóstico de la esteatosis hepática, adoptando p<0,05. RESULTADOS Los adolescentes estudiados presentaron mejoras significativas de la composición corporal, con reducción del porcentaje de grasa total, de la masa gorda total, de la grasa de tronco y del aumento de masa magra, además de reducción del tamaño de los lóbulos del hígado, de los índices de prevalencia de la esteatosis hepática, del colesterol total y del LDL-colesterol. CONCLUSIONES El entrenamiento concurrente fue efectivo por promover mejorías significativas de variables de la composición corporal y del perfil lipídico, además de reducir la prevalencia de la esteatosis hepática. .

OBJETIVO Analisar os efeitos de 20 semanas de treinamento concorrente sobre as variáveis de composição corporal, perfil lipídico e diagnóstico da esteatose hepática em adolescentes obesos. MÉTODOS Realizou-se um ensaio clínico aberto com 34 adolescentes obesos com idades entre 12 e 15 anos. Foram analisados gordura corporal total e de tronco, colesterol total e suas frações (HDL, LDL e VLDL) e triglicérides, sendo realizado exame de ultrassonografia de abdome superior para diagnosticar esteatose hepática. Os participantes foram submetidos ao treinamento concorrente (associação de treino com pesos e exercício aeróbio) três vezes por semana, com duração de uma hora-aula durante 20 semanas. Para o tratamento estatístico, foram realizados o teste t de Student pareado e a análise de frequência, a fim de verificar as reduções relativa e absoluta do diagnóstico da esteatose hepática, adotando-se p<0,05. RESULTADOS Os adolescentes estudados apresentaram melhoras significativas da composição corporal, com diminuição do percentual de gordura total, da massa gorda total, da gordura de tronco e do aumento da massa magra, além de redução do tamanho dos lóbulos do fígado, dos índices de prevalência da esteatose hepática, do colesterol total e LDL-colesterol. CONCLUSÕES O treinamento concorrente foi efetivo por promover melhorias significativas de variáveis da composição corporal e do perfil lipídico, além de reduzir a prevalência da esteatose hepática. .

Intra-abdominal fat is related to metabolic syndrome and non-alcoholic fat liver disease in obese youth.

BACKGROUND: Previous studies have shown an association between adiposity, especially intra-abdominal adipose tissue, and hemodynamic/metabolic comorbidities in adults, however it is not clear in pediatric population. The aim of the study was to analyze the relationship between non-alcoholic fatty liver disease (NAFLD) and components of metabolic syndrome (MS) with values of intra-abdominal (IAAT) and subcutaneous (SCAT) adipose tissue in obese children and adolescents. METHODS: Cross-sectional study. SUBJECTS: 182 obese sedentary children and adolescents (aged 6 to 16 y), identified by the body mass index (BMI). MEASUREMENTS: Body composition and trunk fat by dual-energy X-ray absorptiometry- DXA; lipid profile, blood pressure and pubertal stage were also assessed. NAFLD was classified as absent (0), mild (1), moderate (2) and severe (3), and intra-abdominal and subcutaneous abdominal fat thickness were identified by ultrasound. The MS was identified according to the cut offs proposed by World Health Organization adapted for children and adolescents. The chi-square test was used to compare categorical variables, and the binary logistic regression indicated the magnitude of the associations adjusted by potential cofounders (sex, age, maturation, NAFLD and HOMA-IR). RESULTS: Higher quartile of SCAT was associated with elevated blood pressure (p = 0.015), but not associated with NAFLD (p = 0.665). Higher IAAT was positively associated with increased dyslipidemia (p = 0.001), MS (p = 0.013) and NAFLD (p = 0.005). Intermediate (p = 0.007) and highest (p = 0.001) quartile of IAAT were also associated with dyslipidemia, independently of age, sex, maturation, NAFLD and HOMA-IR (homeostatic model assessment-insulin resistance). CONCLUSION: Obese children and adolescents, with higher IAAT are more prone to develop MS and NAFLD than those with higher values of SCAT, independent of possible confounding variables.