Age and leptinemia association with anxiety and depression symptoms in overweight middle-aged women.

OBJECTIVE: The aim of the study was to investigate the effect of menopause and of postmenopausal stages on depression and anxiety symptoms, and whether these symptoms associate with anthropometric, metabolic, and hormonal parameters in midlife women. METHODS: Postmenopausal women (age 50-65), either at early (EPM, n=33) or late (LPM, n = 23) postmenopause, and 23 premenopausal controls (PreM, age 40-50), matched for BMI with the PM groups, were studied. Blood biochemical and hormonal determinations, bioimpedance anthropometry, and depression and anxiety symptoms (Beck's depression [BDI] and anxiety [BAI] inventories) were conducted. RESULTS: The BAI score was higher in both PM groups than in the PreM group. In contrast, only the LPM group showed a significantly elevated BDI score. All groups presented overweight and abdominal obesity, having similar BMI and waist/hip ratio values. Both PM groups showed insulin resistance, whereas only the LPM group presented decreased skeletal muscle mass and basal metabolic rate. Correlation analysis, including all 79 middle-aged women, showed age, percentage body fat, waist/hip ratio, and leptinemia to correlate positively with the anxiety and depression scores. Multivariate regression showed leptin and age to associate positively with depressive- and anxious-like symptoms. CONCLUSIONS: Postmenopausal women presented impaired body composition, energy expenditure, insulin sensitivity, and mental symptoms, in comparison to similarly overweight premenopausal women. Among all the overweight midlife women, these symptoms were more strongly associated with age and leptin levels than with reproductive aging itself. The data indicate that, among overweight middle-aged women with abdominal obesity, the aging process and the development of leptin resistance are associated with impairment of mental health.

The role of free fatty acids in the inflammatory and cardiometabolic profile in adolescents with metabolic syndrome engaged in interdisciplinary therapy.

The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum fatty acids can be influenced by lifestyle changes and are able to modulate these biomarkers.

Gender-specific effects of intrauterine growth restriction on the adipose tissue of adult rats: a proteomic approach.

BACKGROUND: Intrauterine growth restriction (IUGR) may program metabolic alterations affecting physiological functions and lead to diseases in later life. The adipose tissue is an important organ influencing energy homeostasis. The present study was aimed at exploring the consequences of IUGR on the retroperitoneal adipose tissue of adult male and female rats, using a proteomic approach. METHODS AND RESULTS: Pregnant Wistar rats were fed with balanced chow, either ad libitum (control group) or restricted to 50 % of control intake (restricted group) during the whole gestation. The offspring were weaned to ad libitum chow and studied at 4 months of age. Retroperitoneal fat was analyzed by two-dimensional gel electrophoresis followed by mass spectrometry. Both male and female restricted groups had low body weight at birth and at weaning but normal body weight at adulthood. The restricted males had normal fat pads weight and serum glucose levels, with a trend to hyperinsulinemia. The restricted females had increased fat pads weight with normal glucose and insulin levels. The restricted males showed up-regulated levels of proteasome subunit α type 3, branched-chain-amino-acid aminotransferase, elongation 1- alpha 1, fatty acid synthase levels, cytosolic malate dehydrogenase and ATP synthase subunit alpha. These alterations point to increased proteolysis and lipogenesis rates and favoring of ATP generation. The restricted females showed down-regulated levels of L-lactate dehydrogenase perilipin-1, mitochondrial branched-chain alpha-keto acid dehydrogenase E1, and transketolase. These findings suggest impairment of glycemic control, stimulation of lipolysis and inhibition of proteolysis, pentose phosphate pathway and lipogenesis rates. In both genders, several proteins involved in oxidative stress and inflammation were affected, in a pattern compatible with impairment of these responses. CONCLUSIONS: The proteomic analysis of adipose tissue showed that, although IUGR affected pathways of substrate and energy metabolism in both males and females, important gender differences were evident. While IUGR males displayed alterations pointing to a predisposition to later development of obesity, the alterations observed in IUGR females pointed to a metabolic status of established obesity, in agreement with their increased fat pads mass.

Jussara (Euterpe edulis Mart.) supplementation during pregnancy and lactation modulates the gene and protein expression of inflammation biomarkers induced by trans-fatty acids in the colon of offspring.

Maternal intake of trans-fatty acids (TFAs) in the perinatal period triggers a proinflammatory state in offspring. Anthocyanins contained in fruit are promising modulators of inflammation. This study investigated the effect of Jussara supplementation in the maternal diet on the proinflammatory state of the colon in offspring exposed to perinatal TFAs. On the first day of pregnancy rats were divided into four groups: control diet (C), control diet with 0.5% Jussara supplementation (CJ), diet enriched with hydrogenated vegetable fat, rich in TFAs (T), or T diet supplemented with 0.5% Jussara (TJ) during pregnancy and lactation. We showed that Jussara supplementation in maternal diet (CJ and TJ groups) reduced carcass lipid/protein ratios, serum lipids, glucose, IL-6, TNF-α, gene expression of IL-6R, TNF-αR (P < 0.05), TLR-4 (P < 0.01), and increase Lactobacillus spp. (P < 0.05) in the colon of offspring compared to the T group. The IL-10 (P = 0.035) and IL-10/TNF-α ratio (P < 0.01) was higher in the CJ group than in the T group. The 0.5% Jussara supplementation reverses the adverse effects of perinatal TFAs, improving lipid profiles, glucose levels, body composition, and gut microbiota and reducing low-grade inflammation in the colon of 21-day-old offspring, and could contribute to reducing chronic disease development.

Metabolic profile response to administration of epigallocatechin-3-gallate in high-fat-fed mice.

BACKGROUND: Obesity is associated with increased adipose tissue and glucose intolerance. High-fat diets (HFDs) are known to induce obesity and increase proinflammatory adipokines. The consumption of green tea may improve the health of obese individuals because it contains a potent antioxidant that has effects on body weight, energy expenditure and serum cholesterol concentrations. METHODS: We examined the effects of epigallocatechin-3-gallate (EGCG) (50 mg/kg body weight per day) or saline after 30 or 60 days of treatment. Mice were distributed into four groups: 1) NS: normolipidic diet receiving saline; 2) NE: normolipidic diet receiving EGCG; 3) HFS: high-fat diet receiving saline; 4) HFE: high-fat diet receiving EGCG. RESULTS: We observed that administration of a HFD plus EGCG treatment for 60 days reduced delta weight, the relative weights of the mesenteric adipose tissue (MES), retroperitonial adipose tissue (RET), epididymal adipose tissue (EPI), the sum of the adipose tissues (SAT), reduced triacylglycerol (TG) and improved both high-density lipoprotein (HDL) cholesterol levels and the adiponectin/STA ratio when compared with HFS. CONCLUSIONS: Our results suggest that the chronic administration of EGCG (60 days) promoted a significant improvement in glucose tolerance, decreased adipose tissue deposits, weight mass, TG and HDL-C only when associated with high-fat diet treatment.

Oligofructose supplementation (10%) during pregnancy and lactation does not change the inflammatory effect of concurrent trans fatty acid ingestion on 21-day-old offspring.

BACKGROUND: Previously, we demonstrated that trans fatty acid ingestion during pregnancy and lactation caused a pro-inflammatory effect on the newborn. The opposite effect was described for gestational prebiotic intake. In the present study, we examined whether supplementation of the diet of the dams with 10% of oligofructose with or without hydrogenated vegetable fat during pregnancy and lactation affected the pro-inflammatory status on the pups at age 21 days. METHODS: On the first day of pregnancy, rats were divided into four groups, each of which received one of four diets: a control diet (C group), a control diet supplemented with 10% oligofructose (CF group), a diet enriched with hydrogenated vegetable fat containing trans fatty acids (T group) or a diet enriched with hydrogenated vegetable fat containing trans fatty acids supplemented with 10% oligofructose (TF group). The pups were weighed at birth and at 7, 14 and 21 days of life and were euthanized on post-natal day 21. The serum glucose, insulin and adiponectin concentrations were analyzed. The IL-6, IL-10 and TNF-α contents of the retroperitoneal white adipose tissue, liver, soleus and extensor digital longus muscles were analyzed by ELISA. The results are presented as the means ± standard error of the mean. Statistical significance was assessed using two-way ANOVA, followed by Tukey's test and considered significant at p < 0.05 RESULTS: The body weights of the 21-day old pups in the CF and TF groups were significant lower than those of the C (27% and 21%) and T (25% and 19%, respectively) groups. The serum levels of adiponectin in the CF, T and TF groups were lower than in the C group (41%; 34% and 31%, respectively). In the retroperitoneal adipose tissue, the IL-6 content was increased in TF group relative to the C and CF groups (74% for both), and the TNF-α content was higher in the T and TF groups than in the C group (62% and 98%, respectively). In the liver, the TNF-α (56% and 104%) and IL-10 (52% and 73%) contents were increased in the CF group relative to the C and TF groups. CONCLUSIONS: Supplementation of the diet of the dams with 10% of oligofructose during pregnancy and lactation, independent of supplementation with hydrogenated vegetable fat, adversely affected the development of the offspring and contributed to development of a pro-inflammatory status in the pups on postnatal day 21.

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.

High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations.

BACKGROUND: Adiponectin is the most abundant plasma protein synthesized for the most part in adipose tissue, and it is an insulin-sensitive hormone, playing a central role in glucose and lipid metabolism. In addition, it increases fatty acid oxidation in the muscle and potentiates insulin inhibition of hepatic gluconeogenesis. Two adiponectin receptors have been identified: AdipoR1 is the major receptor expressed in skeletal muscle, whereas AdipoR2 is mainly expressed in liver. Consumption of high levels of dietary fat is thought to be a major factor in the promotion of obesity and insulin resistance. Excessive levels of cortisol are characterized by the symptoms of abdominal obesity, hypertension, glucose intolerance or diabetes and dyslipidemia; of note, all of these features are shared by the condition of insulin resistance. Although it has been shown that glucocorticoids inhibit adiponectin expression in vitro and in vivo, little is known about the regulation of adiponectin receptors. The link between glucocorticoids and insulin resistance may involve the adiponectin receptors and adrenalectomy might play a role not only in regulate expression and secretion of adiponectin, as well regulate the respective receptors in several tissues. RESULTS: Feeding of a high-fat diet increased serum glucose levels and decreased adiponectin and adipoR2 mRNA expression in subcutaneous and retroperitoneal adipose tissues, respectively. Moreover, it increased both adipoR1 and adipoR2 mRNA levels in muscle and adipoR2 protein levels in liver. Adrenalectomy combined with the synthetic glucocorticoid dexamethasone treatment resulted in increased glucose and insulin levels, decreased serum adiponectin levels, reduced adiponectin mRNA in epididymal adipose tissue, reduction of adipoR2 mRNA by 7-fold in muscle and reduced adipoR1 and adipoR2 protein levels in muscle. Adrenalectomy alone increased adiponectin mRNA expression 3-fold in subcutaneous adipose tissue and reduced adipoR2 mRNA expression 2-fold in liver. CONCLUSION: Hyperglycemia as a result of a high-fat diet is associated with an increase in the expression of the adiponectin receptors in muscle. An excess of glucocorticoids, rather than their absence, increase glucose and insulin and decrease adiponectin levels.

Visceral fat decreased by long-term interdisciplinary lifestyle therapy correlated positively with interleukin-6 and tumor necrosis factor-α and negatively with adiponectin levels in obese adolescents.

The purpose of this study was to assess the level of cytokine expression in correlation with visceral and subcutaneous fat in obese adolescents admitted to long-term interdisciplinary weight loss therapy. The study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (18, aged 15-19 years) with body mass indexes greater than the 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. Visceral and subcutaneous fat was analyzed by ultrasonography. Blood samples were collected to analyze tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and adiponectin concentrations that were measured by enzyme-linked immunosorbent assay. The most important finding in the present investigation is that the long-term interdisciplinary lifestyle therapy decreased visceral fat. Positive correlations between IL-6 levels and visceral fat (r = 0.42, P < .02) and TNF-α levels and visceral fat (r = 0.40, P < .05) were observed. Negative correlations between TNF-α levels and subcutaneous fat (r = -0.46, P < .01) and adiponectin levels and subcutaneous fat (r = -0.43, P < .03) were also observed. In addition, we found a positive correlation between TNF-α levels and the visceral to subcutaneous fat ratio (r = 0.42, P < .02) and a negative correlation between adiponectin level and the visceral to subcutaneous fat ratio (r = -0.69, P < .001). Despite the limitation of sample size, our results indicate that the observed massive weight loss (mainly visceral fat) was highly correlated with a decreased inflammatory state, suggesting that the interdisciplinary therapy was effective in decreasing inflammatory markers.

The role of anorexigenic and orexigenic neuropeptides and peripheral signals on quartiles of weight loss in obese adolescents.

Obesity is characterized as an inflammatory state associated with a modification in the pattern of adipokine secretion. The present study aimed to assess the role of anorexigenic and orexigenic neuropeptides and peripheral signals in obese adolescents submitted to 1 year of weight loss interdisciplinary therapy and grouped according to quartiles of weight loss. A total of 111 post-puberty adolescents, with a BMI >95th percentile, were included. Glycemia and lipid profiles were analyzed. Insulin resistance was estimated by HOMA-IR. Cytokine concentrations were measured by ELISA. The results are presented according to quartiles of weight loss: 1st (<2.5 kg)=low; 2nd (2.5-8 kg)=low to moderate; 3rd (8-14 kg)=moderate; and 4th (>14 kg)=massive. The most important finding was that the NPY concentration increased significantly only in the first phase of weight loss. Moreover, α-MSH variation was an independent factor in explaining the NPY changes during the intervention, confirming the role of the α-MSH concentration in the peripheral control of energy balance in obese adolescents. Indeed, BMI reduction was correlated with increased α-MSH (p<0.05). Massive weight loss promoted a significant increase in α-MSH concentration, and hyperleptinemia was reduced after intervention. All together, our findings, which contribute to our understanding of how orexigenic and anorexigenic systems are regulated by weight loss, will provide insight into the pathogenesis and treatment of obesity and other metabolic diseases, especially in obese adolescents.

The role of nutritional profile in the orexigenic neuropeptide secretion in nonalcoholic fatty liver disease obese adolescents.

BACKGROUND: Little progress has been made to identify the central neuroendocrine pathway involved in the energy intake control in nonalcoholic fatty liver disease (NAFLD) patients. OBJECTIVE: To assess the influence of orexigenic neuropeptides in the nutritional aspects of NAFLD obese adolescents submitted to a long-term interdisciplinary approach. METHODS: Fifty adolescents aged 15-19 years, with body mass index at least 95th percentile, consisting of 25 patients without NAFLD and 25 with NAFLD. The NAFLD diagnosis was determined by ultrasonography. Blood samples were collected to analyze glycemia, hepatic transaminases, and lipid profile. Insulin resistance was estimated by Homeostasis Model Assessment Insulin Resistance Index. Neuropeptide Y (NPY) and agouti related protein concentrations were measured by enzyme-linked immunosorbent assay. Analyses of food intake were made by 3 days recordatory inquiry. RESULTS: At baseline conditions, the patients with NAFLD had significantly higher values of body mass, body mass index, visceral fat, triglycerides, VLDL-C, and hepatic transaminases. After the long-term intervention, they presented a significant reduction in these parameters. In both the groups, it was observed a significant decrease in energy intake, macronutrients and dietetic cholesterol. Only the patients with NAFLD presented a positive correlation between the saturated fatty acids intake and the orexigenic neuropeptides NPY and agouti related protein, and carbohydrate with NPY. Indeed, it was observed a positive correlation between energy intake, lipid (%) and saturated fatty acids with visceral fat accumulation. CONCLUSION: Our findings showed an important influence of diet composition in the orexigenic system, being essential consider that the excessive saturated fatty acids intake could be a determinant factor to increase nonalcoholic fatty liver disease.

Relationship between bone mineral density, leptin and insulin concentration in Brazilian obese adolescents.

Despite the epidemic of adolescent obesity, the effect of obesity and hormones on bone mineral accrual during growth is poorly understood. Studies using dual-energy X-ray to examine the effect of obesity on bone mass in children and adolescents have yielded conflicting results. The aim of this study was to explore the combined and independent contributions of body mass index, body composition, leptin, insulin, glucose levels and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) to bone mineral density (BMD) and bone mineral content in a group of Brazilian obese adolescents. This study included 109 post-pubescent obese adolescents. A whole-body dual-energy X-ray absorptiometry scan was performed,using a HOLOGIC QDR4200, to determine whole-body BMD and body composition. Blood samples were collected in the outpatient clinic after an overnight fast, and evaluated for fasting blood glucose and immunoreactive insulin. Leptin levels were assessed with a radioimmunoassay kit. Insulin resistance was assessed by HOMA-IR and the quantitative insulin sensitivity check index. Our results showed that insulin levels and HOMA-IR correlated negatively with BMD and a linear regression analysis showed that serum leptin is inversely associated to BMD adjusted for body mass. In conclusion, our data support the hypothesis that leptin, insulin and HOMA-IR are inversely associated with BMD and play a significant direct role in bone metabolism.

Dietary fish oil did not prevent sleep deprived rats from a reduction in adipose tissue adiponectin gene expression.

Sleep deprivation in humans has been related to weight gain and consequently, increased risk for insulin resistance. In contrast, there is a significant loss of weight in sleep deprived rats suggesting a state of insulin resistance without obesity interference. Thus, we aimed to assess the effects of a rich fish oil dietetic intervention on glucose tolerance, serum insulin and adiponectin, and adipose tissue gene expression of adiponectin and TNF-alpha of paradoxically sleep deprived (PSD) rats. The study was performed in thirty day-old male Wistar randomly assigned into two groups: rats fed with control diet (soybean oil as source of fat) and rats fed with a fish oil rich diet. After 45 days of treatment, the animals were submitted to PSD or maintained as home cage control group for 96 h. Body weight and food intake were carefully monitored in all groups. At the end of PSD period, a glucose tolerance test was performed and the total blood and adipose tissues were collected. Serum insulin and adiponectin were analyzed. Adipose tissues were used for RT-PCR to estimate the gene expression of adiponectin and TNF-alpha. Results showed that although fish oil diet did not exert any effect upon these measurements, PSD induced a reduction in adiponectin gene expression of retroperitoneal adipose tissues, with no change in serum adiponectin concentration or in adiponectin and TNF-alpha gene expression of epididymal adipose tissue. Thus, the stress induced by sleep deprivation lead to a desbalance of adiponectin gene expression.

Effect of fish or soybean oil-rich diets on bradykinin, kallikrein, nitric oxide, leptin, corticosterone and macrophages in carrageenan stimulated rats.

We have previously demonstrated that both n-3 and n-6 polyunsaturated fatty acids (PUFA)-rich diets decrease the acute inflammatory response partially explained by the high corticosterone basal levels. The present study aimed to determine the effect of hyperlipidic diets (PUFA n-3 or n-6) on phagocytosis, hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) release by macrophages, bradykinin (BK) and NO release in the paw inflammatory perfusate and Kallikrein (KK), corticosterone and leptin blood levels. Hyperlipidic diets decreased H(2)O(2) release from macrophages stimulated by carrageenan or phorbol-miristate-acetate (PMA), NO release from macrophage stimulated by carrageenan, BK and NO release in the edema perfusate, KK plasma levels and the increase of serum leptin after carrageenan stimulus. These data show that both fish and soybean oil-rich diets promote similar alterations on inflammatory mediators of carrageenan edema and a causal association with the anti-inflammatory effect of these diets.