Impact of Bariatric Surgery on Circulating Metabolites and Cognitive Performance.

INTRODUCTION: Bariatric surgery is an effective intervention to reduce obesity and improve associated comorbidities. However, its effects on cognitive function are still the subject of debate. Given that the bioavailability of circulating metabolites can influence brain metabolism and cognitive performance, we aimed to assess the effects of bariatric surgery on plasma metabolic profiles and cognitive performance. METHODS: We recruited 26 women undergoing gastric bypass surgery. We conducted anthropometric assessments and collected plasma samples for metabolomic analysis. A set of 4 cognitive tests were used to evaluate cognitive performance. Participants were reevaluated 1 year post-surgery. RESULTS: After surgery, attention capacity and executive function were improved, while immediate memory had deteriorated. Regarding metabolic profile, reduction of beta-tocopherol and increase of serine, glutamic acid, butanoic acid, and glycolic acid were observed. To better understand the relationship between cognitive function and metabolites, a cluster analysis was conducted to identify more homogeneous subgroups based on the cognitive performance. We identified cluster 1, which did not show changes in cognitive performance after surgery, and cluster 2, which showed improved attention and executive function, but reduced performance in the immediate memory test. Thus, cluster 2 was more homogeneous group that replicated the results of non-clustered subjects. Analysis of the metabolic profile of cluster 2 confirmed serine, glutamic acid, and glycolic acid as potential metabolites associated with cognitive performance. CONCLUSIONS: Metabolites identified in this study have potential for biomarkers and alternative therapeutic target to prevent obesity-related cognitive decline. KEY POINTS: • Attention capacity and executive function were improved 12 months post bariatric surgery. • Immediate memory was worsened 12 months post bariatric surgery. • Serine, glutamic acid, and glycolic acid are potential metabolites linked to the alteration of cognitive performance.

Severe Obesity in Women Can Lead to Worse Memory Function and Iron Dyshomeostasis Compared to Lower Grade Obesity.

Objective: Obesity is one of the modifiable risk factors for dementia. Insulin resistance, the abundance of advanced glycated end-products, and inflammation are some of the mechanisms associated with the lower cognitive performance observed in obesity. This study aims to evaluate the cognitive function of subjects with distinct degrees of obesity, comparing class I and II obesity (OBI/II) to class III obesity (OBIII), and to investigate metabolic markers that can distinguish OBIII from OBI/II. Study Design. This is a cross-sectional study, in which 45 females with BMI varying from 32.8 to 51.9 kg/m2 completed a set of 4 cognitive tests (verbal paired-associate test, stroop color, digit span, and Toulouse-Pieron cancellation test) and their plasma metabolites, enzymes, and hormones related to glycemia, dyslipidemia, and liver function, as well as the biomarkers of iron status, were concomitantly analyzed. Results: OBIII showed lower scores in the verbal paired-associate test compared to OBI/II. In other cognitive tests, both groups showed similar performance. OBIII presented a lower iron status compared to OBI/II based on total iron binding capacity, degree of transferrin saturation, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin. The levels of indicators for glycemia, liver function, and lipid metabolism were similar in both groups. Analysis of plasma metabolites showed that OBIII had lower levels of pyroglutamic acid, myoinositol, and aspartic acid and higher levels of D-ribose than OBI/II. Conclusion: Iron is an essential micronutrient for several metabolic pathways. Thus, iron dyshomeostasis observed in severe obesity may aggravate the cognitive impairment by altering metabolic homeostasis and enhancing oxidative stress. These findings can contribute to searching for biomarkers that indicate cognitive performance in the population with obesity.

The role of multicomponent therapy in the metabolic syndrome, inflammation and cardiovascular risk in obese adolescents.

Obesity is characterised by low-grade inflammation, which increases the metabolic syndrome (MetS) and cardiovascular risks. The aim of the present study was to verify the role of multicomponent therapy in controlling the MetS, inflammation and carotid intima-media thickness (cIMT) in obese adolescents. The second aim was to investigate the relationships between adipokines, the MetS parameters and cIMT. A total of sixty-nine obese adolescents participated in the present study and completed 1 year of multicomponent therapy (a combination of strategies involving nutrition, psychology, physical exercise and clinical therapy), and were divided according to their MetS diagnosis as follows: MetS (n 19); non-MetS (n 50). Blood analyses of glucose, lipid and adipokine concentrations (adiponectin, leptin, plasminogen activator inhibitor 1 (PAI-1) and C-reactive protein) were collected. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance, quantitative insulin sensitivity check index and homeostasis model assessment-adiponectin. cIMT and visceral and subcutaneous fat were estimated using ultrasonography. At baseline, the MetS group presented higher waist circumference, glucose and insulin levels, and systolic and median blood pressures compared with the non-MetS group. After therapy, both groups showed improvements in the anthropometric profile, body composition, insulin level, insulin resistance, insulin sensibility, TAG and VLDL-cholesterol, adiponectin, leptin and PAI-1 levels, blood pressure and cIMT. The prevalence of the MetS was reduced from 27·5 to 13·0 %. Metabolic syndrome patients showed resistance in the attenuation of total cholesterol and LDL-cholesterol (LDL-C) levels and leptin:adiponectin and adiponectin:leptin ratios. In the MetS group, the variation in the adiponectin:leptin ratio was correlated with variations in glucose, insulin sensibility, total cholesterol, LDL-c and systolic blood pressure. Additionally, the number of MetS parameters was correlated with the carotid measurement. Moreover, the variation in cIMT was correlated with the variations in insulin sensibility, total cholesterol and LDL-c. For the entire group, the number of MetS alterations was correlated with the leptin level and leptin:adiponectin ratio and adiponectin:leptin ratio after therapy. In conclusion, multicomponent therapy was effective in controlling the MetS, inflammation and cIMT in the obese adolescents. However, the MetS patients showed resistance in the attenuation of the atherogenic lipid profile and leptin:adiponectin ratio and adiponectin:leptin ratio. These results suggest that the MetS patients have increased cardiovascular risks, and that it is important to attempt to control the inflammatory process that occurs due to obesity in clinical practice in order to improve the health of adolescents.

Association of nonalcoholic fatty liver disease with cardiovascular risk factors in obese adolescents: the role of interdisciplinary therapy.

BACKGROUND: Obesity is associated with several cardiovascular risk factors, including nonalcoholic fatty liver disease (NAFLD). These risk factors can induce changes in the arteries such as an increase in the carotid intima-media thickness (cIMT), which contributes to the early development of atherosclerosis. OBJECTIVE: To determine whether NAFLD is associated with an atherogenic lipid profile, inflammatory markers, or cIMT in obese adolescents and to compare the effects of therapeutic lifestyle changes in NAFLD and non-NAFLD groups. METHODS: A total of 79 obese adolescents were divided into two groups: 33 NAFLD and 46 non-NAFLD. They were submitted to an interdisciplinary therapy involving diet exercise and psychological support during the course of 1 year. The cIMT and estimates of fat mass (liver, intra-abdominal, and subcutaneous) were determined ultrasonographically. Body composition, glucose, lipid profile, and adipokines were analyzed before and after the therapy. RESULTS: At baseline, only in the NAFLD group was the homeostasis model assessment of insulin resistance positively correlated with cIMT and triglyceride/high-density lipoprotein cholesterol ratio. Therapy was associated with an increase in adiponectin concentrations and reduced visceral fat, cIMT, leptin, and plasminogen activator inhibitor-1 concentrations, as well as the ratios of total cholesterol/high-density lipoprotein cholesterol and triglycerides/high-density lipoprotein cholesterol in both groups. Only in the non-NAFLD group did therapy result in a reduction in the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and increased high-density lipoprotein cholesterol concentration. CONCLUSIONS: In obese adolescents, NAFLD is associated with cardiovascular risk factors and inflammatory markers of atherosclerosis that were positively correlated with cIMT only in the NAFLD group. Nevertheless, the strength of the present study is that the interdisciplinary therapy effectively improved cIMT and other proinflammatory adipokines in both groups.

Aerobic plus resistance training improves bone metabolism and inflammation in adolescents who are obese.

Obesity is a worldwide epidemic with a high prevalence of comorbidities, including alterations in bone mineral metabolism. The purpose of this yearlong study was to evaluate the role of 2 types of exercise training (aerobic and aerobic plus resistance exercise) on adipokines parameters and bone metabolism in adolescents who are obese. This was a clinical trial study with interdisciplinary weight loss therapy. Forty-two postpubertal adolescents who are obese were subjected to interdisciplinary weight loss therapy with physical exercise, medical monitoring, nutritional intervention, and psychological intervention. Data were collected from serum analyses of leptin, ghrelin, adiponectin, glucose, and insulin. Anthropometric measurements of body composition, bone mineral density, visceral, and subcutaneous fat were also performed. Statistical tests were applied using repeated-measures analysis of variance. Correlations were established using the Pearson test, and dependencies of variables were established using simple linear regression test. Both training types promoted reductions in body mass index, total central, visceral and subcutaneous fat, insulin concentration, and homeostasis model assessment insulin resistance (HOMA-IR) index, but only aerobic plus resistance training showed statistical improvements in the bone mineral content, adiponectin concentration, and lean tissue. Effective reduction in the visceral/subcutaneous ratio, central/peripheral ratio, and leptin concentration was observed. Insulin and the HOMA-IR index were negative predictors of bone mineral content in the combined training group. Moreover, fat distribution was a negative predictor for bone mineral density in both groups. Aerobic plus resistance training promotes a protective role in bone mineral content associated with an improvement in adiponectin and leptin concentrations, favoring the control of the inflammatory state related to obesity in adolescents. Aerobic plus resistance training combined with interdisciplinary interventions provides important strategies to approach obesity, and these strategies may contribute to clinical practice.

Hyperleptinemia: implications on the inflammatory state and vascular protection in obese adolescents submitted to an interdisciplinary therapy.

The low-grade systemic inflammation seen in obesity may affect the actions of some adipose tissue-derived adipokines that are involved in the regulation of vascular function. We sought to verify whether hyperleptinemia may influence the inflammatory and atherogenic responses in obese adolescents undergoing interdisciplinary therapy. Thirty-four obese adolescents underwent interdisciplinary therapy for 1 year. Subjects were considered hyperleptinemic if they had baseline values of leptin above 20 ng/mL for boys and 24 ng/mL for girls. Both groups showed an improvement in body composition and a reduction in carotid intima-media thickness. However, only subjects in the non-hyperleptinemic group showed an increase in adiponectin concentration after therapy. Moreover, leptin concentration was positively correlated with adiponectin and inversely correlated with PAI-1 in this group. Hyperleptinemic state may impair the attenuation of inflammation in obese adolescents undergoing interdisciplinary therapy, particularly by impeding the increase in adiponectin concentration, which is directly involved in vascular protection.

Interaction of bone mineral density, adipokines and hormones in obese adolescents girls submitted in an interdisciplinary therapy.

Obesity is a chronic inflammatory condition with numerous metabolic consequences to the organism, highlighting its influence on bone mass. Therefore, the aim of this study was to verify the role of visceral fat, leptin, adiponectin and ghrelin on bone mineral density in obese post-puberty adolescents girls, submitted to an interdisciplinary therapy. The study involved 20 post-puberty obese adolescent girls: 16±1.5 years of age, 98.9±15.8 kg (weight), 1.60±0.72 m (height) and 37.2±4.8 kg/m2 [body mass index (BMI)]. Anthropometric measurements, body composition, visceral fat, subcutaneous fat, bone mineral density and content were determined. Ghrelin, leptin and adiponectin were analyzed and the leptin/adiponectin ratio was calculated. Our findings showed a significant increase in adiponectin concentration and a reduction in body weight, BMI, total fat mass, visceral and subcutaneous fat. In addition, ghrelin (r2=-0.53; p=0.02) visceral fat (r2=-0.46, p=0.04) (r2 -0.66, p=0.001) and leptin/adiponectin ratio (r2 -0.56, p=0.01) were negative predictors for bone mineral density and content in obese adolescent girls, respectively. It provides a novel physiologically concept that may shed light on the etiology of osteoporosis and help to identify new therapeutic targets. However this should be confirmed in a large cohort study.

The effect of weight loss magnitude on pro-/anti-inflammatory adipokines and carotid intima-media thickness in obese adolescents engaged in interdisciplinary weight loss therapy.

BACKGROUND: Obesity is a chronic disease defined by an excess amount of adipose tissue and presents a low-grade inflammatory state, increasing cardiovascular risk. OBJECTIVE: To assess the effect of weight loss magnitude on the inflammatory profile and carotid intima-media thickness (cIMT) in obese adolescents engaged in interdisciplinary therapy. DESIGN AND PATIENTS: Seventy-seven postpubertal obese adolescents with a BMI greater than the 95th percentile (37·18 ± 5·14), of both genders and between the ages of 14 and 19 years (16·74 ± 1·59) were subjected to a 1-year period of interdisciplinary intervention (nutrition, psychology, physical exercise and clinical support). MEASUREMENTS: Blood samples were collected to analyse glucose, lipid and adipokine concentrations. Body composition, anthropometric profiles and cIMT were measured. The results are presented according to quartiles of weight loss: 1st (≤5·80 kg) = low; 2nd (5·80-10·90 kg) = low to moderate; 3rd (10·90-15·90 kg) = moderate; and 4th (>15·90 kg) = massive. RESULTS: Leptin, the leptin/adiponectin ratio and plasminogen activator inhibitor 1 (PAI-1) were decreased significantly in the low-to-moderate weight loss. The cIMT was reduced in the moderate weight loss. Moreover, adiponectin was increased only in the massive weight loss. Additionally, weight loss was an independent predictor of changes in leptin level, the adiponectin/leptin ratio (A/L ratio) and PAI-1 when the data were adjusted for age and gender. BMI changes were predictors of changes in leptin and PAI-1 levels. A/L ratio was associated with lean body mass (%), independent of gender and age. In addition, changes in A/L ratio were independent predictors of cIMT alterations. CONCLUSIONS: Interdisciplinary therapy may reduce cardiovascular risk factors among adolescents depending on their degree of weight loss (moderate to massive) and when correlated with their inflammatory profile, metabolic state and cIMT.

Long-term effects of aerobic plus resistance training on the adipokines and neuropeptides in nonalcoholic fatty liver disease obese adolescents.

OBJECTIVE: To compare the effects of aerobic training (AT) with aerobic plus resistance training (AT+RT) in nonalcoholic fatty liver disease (NAFLD) obese adolescents. DESIGN: Long-term interdisciplinary weight-loss therapy (1 year of clinical, nutritional, psychological, and exercise-related intervention). PARTICIPANTS: Fifty-eight postpubertal obese adolescents were randomized to AT or AT+RT according to NAFLD diagnosis. Adipokine and neuropeptide concentrations were measured by enzyme-linked immunosorbent assay, visceral fat by ultrasound, and body composition by plethysmography. RESULTS: The NAFLD group that followed the AT+RT protocol presented lower insulin, homeostasis model assessment-insulin resistance (HOMA-IR), and alanine transaminase (ALT) values after intervention compared with AT. It was verified that there was a higher magnitude of change in the subcutaneous fat, glycemia, total cholesterol (TC), low-density lipoprotein-cholesterol, ALT, and adiponectin in response to AT+RT than in the control group (AT). All patients who underwent the AT+RT exhibited significantly higher adiponectin, leptin, and Δadiponectin and lower melanin-concentrating hormone (MCH) concentrations after therapy compared with the AT group. In the simple linear regression analysis, changes in glycemia, insulin, and HOMA-IR were independent predictors of significant improvement in adiponectin concentration. Indeed, ΔAST (aspartate transaminase) and ΔGGT (γ-glutamyl transpeptidase) were independent predictors of ΔALT, while Δfat mass and ΔAgRP (agouti-related protein) were independent predictors of ΔMCH. Although the number of patients was limited, we showed for the first time the positive effects of AT+RT protocol in a long-term interdisciplinary therapy to improve inflammatory biomarkers and to reduce orexigenic neuropeptide concentrations in NAFLD obese adolescents. CONCLUSION: The long-term interdisciplinary therapy with AT+RT protocol was more effective in significantly improving noninvasive biomarkers of NAFLD that are associated with the highest risk of disease progression in the pediatric population.

Influence of visceral and subcutaneous fat in bone mineral density of obese adolescents.

OBJECTIVE: To verify the influence of visceral and subcutaneous fat, as well adipokines in bone mineral density (BMD) in obese adolescents. SUBJECTS AND METHODS: The study involved 125 postpubertal obese adolescents (45 boys and 80 girls). Anthropometric measurements, body composition, visceral and subcutaneous fat, and BMD were determined. Leptin, adiponectin, and insulin levels also analyzed. RESULTS: Data demonstrated a negative relationship between BMD with insulin resistance, visceral fat and leptin concentration; and bone mineral content with visceral/subcutaneous ratio. Positive association between BMD and subcutaneous fat was observed. CONCLUSIONS: Visceral fat and insulin resistance, as well as visceral/subcutaneous ratio and leptin concentration, were negative predictors of BMD in boys and girls, respectively. However, subcutaneous fat had a protective influence in BMD only in boys.

The role of pro/anti-inflammatory adipokines on bone metabolism in NAFLD obese adolescents: effects of long-term interdisciplinary therapy.

To investigate the role of pro- and anti-inflammatory adipokines in the bone metabolism of non-alcoholic fatty liver disease (NAFLD) obese adolescents as well as the effects of long-term interdisciplinary therapy on metabolic-related risk factors. Forty post-puberty obese adolescents were randomly assigned into two groups: (1) NAFLD group and (2) non-NAFLD group (diagnosis by ultrasonography) and submitted to a weight loss therapy. Body composition was analyzed by air displacement plethysmography, bone mineral density (BMD) and content by dual-energy X-ray absorptiometry, blood samples were collected to measure lipid profile, hepatic enzymes, and adipokines. Leptin and adiponectin concentrations were measured by ELISA. A decrease in total body mass, BMI, body fat, visceral and subcutaneous fat, insulin concentration, HOMA-IR, total cholesterol and an increase in lean body mass were observed in both groups after therapy. It was found positive correlation between the Δ BMD and the Δ fat mass (%) (r = 0.31, P = 0.01) and negative correlations between Δ BMC with Δ HOMA-IR (r = -0.34, P = 0.02) and Δ HOMA-IR with Δ leptin (r = -0.34, P = 0.02). In addition, increased levels of adiponectin and reduction in leptin concentrations were observed in NAFLD group. In the simple regression analysis, the HOMA-IR was an independent predictor changes in BMC in total obese adolescents and in the non-NAFLD group. One year of interdisciplinary weight loss therapy for obese adolescents with or without NAFLD, could regulate bone mineral metabolism as result of an increased BMC and improved inflammatory state.

Influence of visceral and subcutaneous fat in bone mineral density of obese adolescents / A influência da gordura visceral e subcutânea na densidade mineral óssea de adolescentes obesos

OBJECTIVE: To verify the influence of visceral and subcutaneous fat, as well adipokines in bone mineral density (BMD) in obese adolescents. SUBJECTS AND METHODS: The study involved 125 postpubertal obese adolescents (45 boys and 80 girls). Anthropometric measurements, body composition, visceral and subcutaneous fat, and BMD were determined. Leptin, adiponectin, and insulin levels also analyzed. RESULTS: Data demonstrated a negative relationship between BMD with insulin resistance, visceral fat and leptin concentration; and bone mineral content with visceral/subcutaneous ratio. Positive association between BMD and subcutaneous fat was observed. CONCLUSIONS: Visceral fat and insulin resistance, as well as visceral/subcutaneous ratio and leptin concentration, were negative predictors of BMD in boys and girls, respectively. However, subcutaneous fat had a protective influence in BMD only in boys.

OBJETIVO: Verificar a influência da gordura visceral e subcutânea, assim como das adipocinas na densidade mineral óssea (DMO) em adolescentes obesos. SUJEITOS E MÉTODOS: O estudo envolveu 125 adolescentes obesos pós-púberes. Medidas antropométricas, composição corporal, gordura visceral e subcutânea e DMO foram determinadas. Níveis de leptina, adiponectina e insulina foram analisados. RESULTADOS:Os dados demonstraram associação negativa entre DMO com resistência insulínica, gordura visceral e concentração de leptina; e conteúdo mineral ósseo com a razão visceral/subcutânea. Associação positiva entre DMO e gordura subcutânea foi observada. CONCLUSÕES: Gordura visceral, resistência insulínica, razão visceral/subcutânea e concentração de leptina foram preditores negativos da DMO em meninos e meninas, respectivamente. Entretanto, a gordura subcutânea demonstrou exercer influência positivamente na DMO somente nos meninos.

Obese adolescents with eating disorders: analysis of metabolic and inflammatory states.

OBJECTIVE: The purpose of the present investigation was to compare the effect of interdisciplinary therapy on the physical and metabolic profiles, including body composition, insulin resistance and sensitivity as well as adiponectin and leptin concentrations, of obese adolescents with and without eating disorder symptoms. METHODS: A total of 83 obese adolescents (28 with and 55 without eating disorder symptoms) were enrolled for 1 year of interdisciplinary weight-loss therapy (clinical, nutritional, exercise, physiotherapy and psychological). Bulimic and binge eating symptoms were measured by the Bulimic Investigatory Test, Edinburgh, and the Binge Eating Scale, respectively. Leptin and adiponectin concentrations were measured with enzyme-linked immunosorbent assay kits. Visceral and subcutaneous fat were assessed by ultrasonography. RESULTS: Both groups demonstrated improved body mass, body mass index, body fat (%), lean mass, visceral fat, subcutaneous fat, homeostasis model assessment insulin-resistance index (HOMA-IR), quantitative insulin sensitivity check index, total cholesterol, LDL-cholesterol, VLDL, triglycerides, adiponectin and leptin concentrations after therapy. We found a positive correlation between leptin concentrations and subcutaneous fat in the control group and a negative correlation between adiponectin concentrations and HOMA-IR and fat mass (%). The prevalence of obese adolescents with eating disorders was reduced by 89% after 1 year of interdisciplinary therapy. CONCLUSION: The eating disorder symptoms did not impair the metabolic state during weight loss therapy of obese adolescents. Additionally, long-term interdisciplinary therapy was effective in reducing the chances of developing several co-morbidities in both groups.