Peripheral insulin resistance is early, progressive, and correlated with cachexia in Walker-256 tumor-bearing rats.

Insulin (INS) resistance is often found in cancer-bearing, but its correlation with cachexia development is not completely established. This study investigated the temporal sequence of the development of INS resistance and cachexia to establish the relationship between these factors in Walker-256 tumor-bearing rats (TB rats). INS hepatic sensitivity and INS resistance-inducing factors, such as free fatty acids (FFA) and tumor necrosis factor-α (TNF-α), were also evaluated. Studies were carried out on Days 2, 5, 8, and/or 12 after inoculation of tumor cells in rats. The peripheral INS sensitivity was assessed by the INS tolerance test and the INS hepatic sensitivity in in situ liver perfusion. TB rats with 5, 8, and 12 days of tumor, but not 2 days, showed decreased peripheral INS sensitivity (INS resistance), retroperitoneal fat, and body weight, compared to healthy rats, which were more pronounced on Day 12. Gastrocnemius muscle wasting was observed only on Day 12 of tumor. The peripheral INS resistance was significantly correlated (r = -.81) with weight loss. Liver INS sensitivity of TB rats with 2 and 5 days of tumor was unchanged, compared to healthy rats. TB rats with 12 days of tumor showed increased plasma FFA and increased TNF-α in retroperitoneal fat and liver, but not in the gastrocnemius, compared to healthy rats. In conclusion, peripheral INS resistance is early, starts along with fat and weight loss and before muscle wasting, progressive, and correlated with cachexia, suggesting that it may play an important role in the pathogenesis of the cachectic process in TB rats. Therefore, early correction of INS resistance may be a therapeutic approach to prevent and treat cancer cachexia.

Phenylhydrazine-induced anaemia reduces subcutaneous white and brown adipose tissues in hypothalamic obese rats.

NEW FINDINGS: What is the central question of this study? Can an anaemic state modify adiposity and metabolic parameters in hypothalamic obese rats? What is the main finding and its importance? Hypothalamic obese rats do not display iron deficiency. However, the pharmacological induction of anaemia in hypothalamic obese rats resulted in reduced adiposity, characterized by a decrease in subcutaneous white and brown adipose tissue depots. These findings suggest that iron imbalance in obesity may elevate lipolysis. ABSTRACT: Iron imbalance is frequent in obesity. Herein, we evaluated the impact of anaemia induced by phenylhydrazine on adiposity and metabolic state of hypothalamic obese rats. Hypothalamic obesity was induced by high doses of monosodium glutamate (MSG; 4 g/kg) administered to neonatal male rats (n = 20). Controls (CTL; non-obese rats) received equimolar saline (n = 20). Rats were weaned at 21 days of life. At 70 days, half of the rats received three intraperitoneal doses of phenylhydrazine (PHZ; 40 mg/kg/dose) or saline solution. Body weight and food intake were followed for 4 weeks after PHZ administration. At 92 days, rats were killed and blood was collected for microcapillary haematocrit (Hct) analysis and plasma quantification of glucose, triglycerides, total cholesterol and iron levels. The liver, the spleen, and the white (WAT) and brown (BAT) adipose tissues were excised, weighed and used for histology. MSG-treated rats developed obesity, hypertriglyceridaemia and insulin resistance, compared to CTL rats, without changes in iron levels and Hct. PHZ administration reduced plasma iron levels and promoted similar tissue injuries in the spleen and liver from MSG and CTL rats. However, in MSG-treated rats, PHZ decreased fasting glucose levels and Hct, as well as diminishing the subcutaneous WAT and BAT mass. Although MSG-obesity does not affect plasma iron levels and Hct by itself, PHZ-induced anaemia associated with obesity induces a marked drop in subcutaneous WAT and BAT mass, suggesting that iron imbalance may lead to increased lipolytic responses in obese rats, compared to lean rats.

Myeloperoxidase as an important predictor of cardiovascular risk in individuals with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is an inflammatory disease with joint manifestations. In the presence of extra-articular manifestations, the morbidity and severity of the disease increase. Glucocorticoid is used as a treatment and may result in side effects related to cardiovascular risk. METHODS: This was a cross-sectional study including 59 volunteers with rheumatoid arthritis receiving treatment at a hospital of Campos Gerais that aimed to establish the relation between cardiovascular risk, glucocorticoid treatment and myeloperoxidase in these patients. Subjects were divided into two groups: using (n = 39) and without glucocorticoids (n = 20). They underwent clinical evaluation, physical examination and blood samples were taken. Statistical analysis was performed using Student's t test and Mann-Whitney test. Logistic regression was performed to assess the cardiovascular risk. The significance level was 5% (α = 0.05). Calculations were performed using the Statistical Package for the Social Science version 21.0. RESULTS: There has been a significant difference between groups in blood glucose values (p = 0.012), which can be explained by the different percentage of diabetic patients in the groups. When assessing cardiovascular risk using the predictors of glucocorticoid dose, time of glucocorticoid use, myeloperoxidase, and C-reactive protein together, these were responsible for significantly predicting this risk (p = 0.015). CONCLUSION: A significant relation between the predictor myeloperoxidase alone was also demonstrated (p = 0.037), it may be an important predictor of cardiovascular risk among individuals with rheumatoid arthritis.

Swimming training reduces glucose-amplifying pathway and cholinergic responses in islets from lean- and MSG-obese rats.

Here, we investigate the effects of exercise training on glucose- and cholinergic-induced insulin secretion in pancreatic islets from obese and lean rats. Male Wistar rats were treated with monosodium glutamate (MSG) for the first 5 days of life, while control (CON) rats received saline. At 21 days, the rats were divided into exercised (EXE) and sedentary (SED) groups. The EXE rats swam for 30 minutes, three times/week, for 10 weeks. After this, MSG-SED rats showed hyperglycaemia, hypertriglyceridaemia and hyperinsulinaemia. Besides, islets from MSG-SED rats exhibited increased glucose-stimulated insulin secretion (GSIS), followed by impaired glucose sensitivity, absence of glucose-amplifying pathway and weak cholinergic response. In contrast, adiposity, hyperinsulinaemia and hypertriglyceridaemia were reduced in MSG-EXE rats. Moreover, islets from MSG-EXE rats exhibited lower GSIS and improved islet glucose sensitivity, without restoration of the glucose-amplifying pathway or alteration in the weak cholinergic effect of these islets. In islets from CON-EXE rats we also observed reduced GSIS and absence of glucose-amplifying effects and an accentuated reduction in cholinergic insulinotropic responses, without effect on glucose sensitivity in pancreatic islets from this group. Neither obesity nor exercise modified Muscarinic Receptor 3 (M3R) immunocontent or its downstream pathways (PKC and PKA). Moreover, only CON-EXE showed increased GSIS in the presence of calcium blocker, Thapsigargin. In conclusion, swimming training reduces GSIS and cholinergic responsiveness in isolated pancreatic islets from lean and hypothalamic obese rats, which could be due to the inhibition of glucose-amplifying pathways.

Physical exercise associated with vitamin D chronic supplementation reduces kidney injury induced by monosodium glutamate.

The aim was to evaluate the effects of chronic vitamin D (VD) supplementation associated with regular swimming over renal histomorphometric aspects in obese rats. Thirty Wistar male rats (5 days old) were used. Twenty four rats were given subcutaneous injections of monosodium glutamate (MSG; 4 g/kg), and six control rats were given an equimolar saline solution. At 21-days-old, the MSG-treated rats were randomly distributed among sedentary animals (S) and exercised (E, swimming; 3x/week). These groups were subdivided into groups orally supplemented with VD (12 µg/kg; 3x/week) or not supplemented (NS), totaling Five experimental groups (n = 6 rats/group): MSG, MSG-SVD, MSG-ENS, MSG-EVD and control groups. In MSG-obese rats, there was such as a decrease in the diameter of the, glomerular tuft, Bowman's capsule, Bowman's space areas, and renal cortical thickness, compared to the control group. In MSG-SVD, MSG-ENS, and MSG-EVD animals, there was an increase in the cortical thickness in relation to the MSG group. In MSG-ENS and MSG-EVD animals, there was a reduction of tubular degeneration in relation to the MSG group. We conclude that physical exercise associated with Vitamin D supplementation can prevent of renal injury, increasing the thickness of the renal cortex and decrease the tubular degeneration.

The effect of chronic oral vitamin D supplementation on adiposity and insulin secretion in hypothalamic obese rats.

Reduced plasma vitamin D (VD) levels may contribute to excessive white adipose tissue, insulin resistance (IR) and dyslipidaemia. We evaluated the effect of chronic oral VD supplementation on adiposity and insulin secretion in monosodium glutamate (MSG)-treated rats. During their first 5 d of life, male neonate rats received subcutaneous injections of MSG (4 g/kg), while the control (CON) group received saline solution. After weaning, groups were randomly distributed into VD supplemented (12 µg/kg; three times/week) and non-supplemented (NS) rats, forming four experimental groups (n 15 rats/group): CON-NS, CON-VD, MSG-NS and MSG-VD. At 76 d of life, rats were submitted to an oral glucose tolerance test (OGTT; 2 g/kg), and at 86 d, obesity, IR and plasma metabolic parameters were evaluated. Pancreatic islets were isolated for glucose-induced insulin secretion (GIIS), cholinergic insulinotropic response and muscarinic 3 receptor (M3R), protein kinase C (PKC) and protein kinase A (PKA) expressions. Pancreas was submitted to histological analyses. VD supplementation decreased hyperinsulinaemia (86 %), hypertriacylglycerolaemia (50 %) and restored insulin sensibility (89 %) in MSG-VD rats, without modifying adiposity, OGTT or GIIS, compared with the MSG-NS group. The cholinergic action was reduced (57 %) in islets from MSG-VD rats, without any change in M3R, PKA or PKC expression. In conclusion, chronic oral VD supplementation of MSG-obese rats was able to prevent hyperinsulinaemia and IR, improving triacylglycerolaemia without modifying adiposity. A reduced cholinergic pancreatic effect, in response to VD, could be involved in the normalisation of plasma insulin levels, an event that appears to be independent of M3R and its downstream pathways.

Litter Size Reduction Induces Metabolic and Histological Adjustments in Dams throughout Lactation with Early Effects on Offspring.

In the present study we analyzed morphological and metabolic alterations in dams nursing small litters and their consequences to offspring throughout lactation. Offspring sizes were adjusted to Small Litter (SL, 3 pups/ dam) and Normal Litter (NL, 9 pups/ dam). Body weight, food intake, white adipose tissue (WAT) content, histological analysis of the pancreas, mammary gland (MG) and brown adipose tissue (BAT) as well as, plasma parameters and milk composition were measured in dams and pups on the 7th, 14th and 21st days of lactation. In general, SL-dams presented higher body weight and retroperitoneal fat content, elevated fat infiltration in BAT, reduced islets size and hyperglycemia throughout lactation in relation to NL-dams (p<0.05). Moreover, MG from SL-dams had reduced alveoli development and high adipocytes content, resulting in milk with elevated energetic value and fat content in relation to NL-dams (p<0.05). Maternal states influenced offspring anthropometric conditions during lactation, offspring-SL displayed higher body weight and growth, hyperglycemia, augmented lipid deposition in BAT and elevated islet. Thus, maternal histological and metabolic changes are due to modifications to nursing small litters and reinforce the importance of preserving maternal health during lactation avoiding early programming effects on offspring preventing metabolic consequences later in life.

Metabolic dysfunction in a rat model of early-life scarcity-adversity: Modulatory role of cafeteria diet.

NEW FINDINGS: What is the central question of this study? Early-life adversity is associated with increased risk for obesity and metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination of both. What is the main finding and its importance? Early-life adversity increases vulnerability to later-life obesity and metabolic dysfunction, indicating that genetics and adult lifestyle are not the only determinants of obesity and related metabolic dysfunction. Moreover, consumption of cafeteria diet exacerbated metabolic dysfunction associated with early-life adversity, suggesting that poor dietary choices might have a bigger impact in the context of early-life adversity. ABSTRACT: Early-life adversity has become recognized as an important factor contributing to adult obesity and associated metabolic dysfunction. However, it is unclear whether obesity and metabolic dysfunction associated with early-life adversity result from coping strategies to deal with adversity-related emotional dysregulation, a direct programming of systems regulating metabolic function, or a combination. Interestingly, both early-life adversity and later-life dietary choices affect immune function, favouring pro-inflammatory mechanisms that are associated with obesity-related metabolic dysfunction. To investigate the unique and/or interactive effects of early-life adversity and later-life dietary choices for increased vulnerability to obesity and metabolic dysfunction, and specifically the role of the immune system in this vulnerability, we combined a naturalistic rat model of early-life scarcity-adversity with a rat model of obesity, the cafeteria diet. Our results indicate that early-life adversity alone induces insulin resistance, reduces pancreatic insulin secretion, plasma concentrations of triglycerides and cholesterol, and increases fasting glucose and tumour necrosis factor-α plasma concentrations. Importantly, animals exposed to adverse rearing were more vulnerable to metabolic dysregulation associated with the cafeteria diet, given that they consumed more energy, showed more severe hepatic steatosis and increased concentrations of the pro-inflammatory cytokine interleukin-1ß than normally reared animals fed the cafeteria diet. Together, our results suggest that early-life adversity negatively programmes physiological systems that regulate metabolic function and increases vulnerability to obesity and metabolic dysfunction in adulthood. These results highlight the intrinsic relationship between the quality of the early postnatal environment and later-life dietary choices on adult health outcomes.

Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats.

Here, we evaluated whether the exposure of rats to a cafeteria diet pre- and/or post-weaning, alters histological characteristics in the White Adipose Tissue (WAT), Brown Adipose Tissue (BAT), and liver of adult male offspring. Female Wistar rats were divided into Control (CTL; fed on standard rodent chow) and Cafeteria (CAF; fed with the cafeteria diet throughout life, including pregnancy and lactation). After birth, only male offspring (F1) were maintained and received the CTL or CAF diets; originating four experimental groups: CTL-CTLF1; CTL-CAFF1; CAF-CTLF1; CAF-CAFF1. Data of biometrics, metabolic parameters, liver, BAT and WAT histology were assessed and integrated using the Principal Component Analysis (PCA). According to PCA analysis worse metabolic and biometric characteristics in adulthood are associated with the post-weaning CAF diet compared to pre and post weaning CAF diet. Thus, the CTL-CAFF1 group showed obesity, higher deposition of fat in the liver and BAT and high fasting plasma levels of glucose, triglycerides and cholesterol. Interestingly, the association between pre and post-weaning CAF diet attenuated the obesity and improved the plasma levels of glucose and triglycerides compared to CTL-CAFF1 without avoiding the higher lipid accumulation in BAT and in liver, suggesting that the impact of maternal CAF diet is tissue-specific.

Histological and Metabolic State of Dams Suckling Small Litter or MSG-Treated Pups.

Lactation is an important function that is dependent on changes in the maternal homeostasis and sustained by histological maternal adjustments. We evaluated how offspring manipulations during the lactational phase can modulate maternal morphologic aspects in the mammary gland, adipose tissue, and pancreatic islets of lactating dams. Two different models of litter-manipulation-during-lactation were used: litter sizes, small litters (SL) or normal litters (NL) and subcutaneous injections in the puppies of monosodium glutamate (MSG), or saline (CON). SL Dams and MSG Dams presented an increase in WAT content and higher plasma levels of glucose, triglycerides, and insulin, in relation to NL Dams and CON Dams, respectively. The MG of SL Dams and MSG Dams presented a high adipocyte content and reduced alveoli development and the milk of the SL Dams presented a higher calorie and triglyceride content, compared to that of the NL Dams. SL Dams presented a reduction in islet size and greater lipid droplet accumulation in BAT, in relation to NL Dams. SL Dams and MSG Dams present similar responses to offspring manipulation during lactation, resulting in changes in metabolic parameters. These alterations were associated with higher fat accumulation in BAT and changes in milk composition only in SL Dams.

Baccharis dracunculifolia methanol extract enhances glucose-stimulated insulin secretion in pancreatic islets of monosodium glutamate induced-obesity model rats.

CONTEXT: Obesity is the main risk factor for type 2 diabetes mellitus. Secondary metabolites with biological activities and pharmacological potential have been identified in species of the Baccharis genus that are specifically distributed in the Americas. OBJECTIVE: This study evaluated the effects of methanol extracts from Baccharis dracunculifolia DC. Asteraceae on metabolic parameters, satiety, and growth in monosodium glutamate (MSG) induced-obesity model rats. MATERIALS AND METHODS: MSG was administered to 32 newborn rats (4 mg/g of body weight) once daily for 5 consecutive days. Four experimental groups (control, control + extract, MSG, and MSG + extract) were treated for 30 consecutive days with 400 mg/kg of B. dracunculifolia extract by gavage. Biochemical parameters, antioxidant activity, total extract phenolic content (methanolic, ethanolic, and acetone extractions), and pancreatic islets were evaluated. RESULTS: High levels of phenolic compounds were identified in B. dracunculifolia extracts (methanol: 46.2 ± 0.4 mg GAE/L; acetate: 70.5 ± 0.5 mg GAE/L; and ethanol: 30.3 ± 0.21 mg GAE/L); high antioxidant activity was detected in B. dracunculifolia ethanol and methanol extracts. The concentration of serum insulin increased 30% in obese animals treated with extract solutions (1.4-2.0 µU/mL, p < 0.05). Insulin secretion in pancreatic islets was 8.3 mM glucose (58%, p < 0.05) and 16.7 mM (99.5%, p < 0.05) in rats in the MSG + extract and MSG groups, respectively. DISCUSSION AND CONCLUSION: Treatment with B. dracunculifolia extracts protected pancreatic islets and prevented the irreversible cellular damage observed in animals in obesity and diabetes models.

Effects of l-arginine and creatine administration on spatial memory in rats subjected to a chronic variable stress model.

CONTEXT: Chronic stress results from repeated exposure to one or more types of stressors over a period, ranging from days to months, and can be associated with physical, behavioral, and neuropsychiatric manifestations. Some physiological alterations resulting from chronic stress can potentially cause deficits on spatial learning and memory. OBJECTIVE: This study investigated the effects of chronic variable stress (CVS) and administration of l-arginine and creatine on spatial memory in rats. Furthermore, body, heart, adrenal weight, and plasma glucose and corticosterone levels were analyzed. MATERIAL AND METHODS: Male Wistar rats were subjected to a CVS model for 40 days and evaluated for spatial memory after the stress period. Chronically stressed animals were treated daily by gavage with: 0.5% carboxymethylcellulose (Group Cs), 500 mg/kg l-arginine (Group Cs/La), 300 mg/kg creatine (Group Cs/Cr); and 500 mg/kg l-arginine and 300 mg/kg creatine (Group Cs/La + Cr) during the entire experimental period. RESULTS: Our results showed that animals in the Cs/Cr and Cs/La + Cr groups presented significantly decreased corticosterone levels compared to group Cs (p < 0.05); animals in group Cs/Cr were more efficient in finding the platform, in the working memory task, compared to all other groups (p < 0.01); and animals in group Cs/La + Cr significantly improved in reference memory retention compared to controls (p < 0.05). DISCUSSION AND CONCLUSION: Overall, these results demonstrated that a single administration of creatine improves working memory efficiency, and, when co-administrated with l-arginine, improves reference memory retention, a phenomenon that is possibly associated with increased creatine/phosphocreatine levels and l-arginine-derived NO synthesis.

Glycolytic and mitochondrial metabolism in pancreatic islets from MSG-treated obese rats subjected to swimming training.

BACKGROUNDS/AIMS: Obese rats obtained by neonatal monosodium glutamate (MSG) administration present insulin hypersecretion. The metabolic mechanism by which glucose catabolism is coupled to insulin secretion in the pancreatic ß-cells from MSG-treated rats is understood. The purpose of this study was to evaluate glucose metabolism in pancreatic islets from MSG-treated rats subjected to swimming training. METHODS: MSG-treated and control (CON) rats swam for 30 minutes (3 times/week) over a period of 10 weeks. Pancreatic islets were isolated and incubated with glucose in the presence of glycolytic or mitochondrial inhibitors. RESULTS: Swimming training attenuated fat pad accumulation, avoiding changes in the plasma levels of lipids, glucose and insulin in MSG-treated rats. Adipocyte and islet hypertrophy observed in MSG-treated rats were attenuated by exercise. Pancreatic islets from MSG-treated obese rats also showed insulin hypersecretion, greater glucose transporter 2 (GLUT2) expression, increased glycolytic flux and reduced mitochondrial complex III activity. CONCLUSION: Swimming training attenuated islet hypertrophy and normalised GLUT2 expression, contributing to a reduction in the glucose responsiveness of pancreatic islets from MSG-treated rats without altering glycolytic flux. However, physical training increased the activity of mitochondrial complex III in pancreatic islets from MSG-treated rats without a subsequent increase in glucose-induced insulin secretion.

Moderate exercise restores pancreatic beta-cell function and autonomic nervous system activity in obese rats induced by high-fat diet.

BACKGROUND/AIMS: Metabolic syndrome has been identified as one of the most significant threats to human health in the 21(st) century. Exercise training has been shown to counteract obesity and metabolic syndrome. The present study aimed to investigate the effects of moderate exercise training on pancreatic beta-cell function and autonomic nervous system (ANS) activity in rats fed a high-fat diet (HFD). METHODS: Weaning rats were divided into four groups: rats fed a standard chow or HFD (sedentary, Control-SED and HFD-SED; or exercised, Control-EXE and HFD-EXE, respectively). Exercised rats ran (from 21- to 91-days-old) for 60 minutes (3 times/week) over a 10-week period. Glucose and insulin tolerance tests were performed. Pancreatic islets were isolated to study glucose-induced insulin secretion (GIIS). Parasympathetic and sympathetic nerve electrical signals were measured, and liver samples were processed and histologically analyzed. RESULTS: Exercise prevented obesity, insulin resistance, and liver steatosis as well as improved total cholesterol, ALT, and AST levels. Islets from HFD rats showed insulin hypersecretion which was ameliorated by exercise. Exercise decreased vagal nerve activity in the HFD-EXE group and increased the activity of the sympathetic nervous system in both exercised groups. CONCLUSION: Exercise prevents obesity and liver steatosis and restores pancreatic beta-cell function and ANS activity in HFD-obese rats.

Impact of Roux-en-Y Gastric Bypass and Vertical Gastrectomy on weight loss: a retrospective and longitudinal study in the State of Paraná, Brazil.

AIM: to compare the impact of Roux's Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) techniques on body weight reduction over 1 and 5 years after bariatric surgery in obese patients in the state of Paraná. METHODS: longitudinal and retrospective study, conducted between January 2010 and December 2013, with 737 patients of both sexes submitted to RYGB or SG and evaluated in the preoperative, 1 and 5 years after bariatric surgery (BS). Age, height, body weight, Body Mass Index (BMI), biochemical and pressure parameters were recorded. RESULTS: of the total of patients, men represented lower frequency, were slightly older, with higher body weight, BMI and worse metabolic and pressure conditions than women in pre-BS (p<0.05). Regardless of sex, RYGB and SG were effective in promoting body weight reduction and BMI in 1 and 5 years after BS; the RYGB technique had greater impact on these variables in both sexes (p<0.05). The highest percentage of lost weight was observed in women who underwent the RYGB technique in the first year after BS. Five years after BS, the RYGB technique promoted a higher rate of body weight reduction in men and women compared to the SG technique (p<0.05). CONCLUSION: regardless of sex, the RYGB technique promotes a higher degree of body weight reduction and BMI over time compared to the SG; having its biggest impacts in the 1 year after BS, especially in women.

Body mass index and abdominal waist values are related to increased cardiometabolic risk in schoolchildren aged five to ten years.

OBJECTIVE: To evaluate the frequency of obesity and cardiometabolic risk in schoolchildren under ten years old. METHODS: This is a cross-sectional study with schoolchildren (n=639) aged five to ten years in a municipally of southern of Brazil. The cardiometabolic risk was calculated from values of body mass index (BMI), waist circumference (WC), diastolic (DBP) and systolic blood pressure (SBP), blood glucose levels, triglycerides and total cholesterol (TC). Odds ratio (OR), Spearman correlation and principal component analysis (PCA) were analyzed. RESULTS: Independent of sex, elevated WC and BMI were related to higher values of SBP, DBP, and TC in schoolchildren. The frequency of cardiometabolic risk was 6.0% in girls and 9.9% in boys. Schoolchildren with elevated values of SBP, triglycerides and TC presented high OR for cardiometabolic risk. PCA indicated that schoolchildren with high WC (p>80) presented more frequently altered glucose levels, triglycerides, and TC. CONCLUSIONS: Obesity, especially when associated with elevated WC, is related to metabolic dysfunctions and cardiometabolic risk in schoolchildren under ten years of age. These findings indicate the urgency of stablishing metabolic risk for this age group, enabling early diagnosis and adequate treatment, to prevent the development of diabetes and cardiovascular dysfunction throughout life.

Variants of the HNF1α gene: A molecular approach concerning diabetic patients from southern Brazil.

Maturity Onset Diabetes of the Young (MODY) presents monogenic inheritance and mutation factors which have already been identified in six different genes. Given the wide molecular variation present in the hepatocyte nuclear factor-1α gene (HNF1α) MODY3, the aim of this study was to amplify and sequence the coding regions of this gene in seven patients from the Campos Gerais region, Paraná State, Brazil, presenting clinical MODY3 features. Besides the synonymous variations, A15A, L17L, Q141Q, G288G and T515T, two missense mutations, I27L and A98V, were also detected. Clinical and laboratory data obtained from patients were compared with the molecular findings, including the I27L polymorphism that was revealed in some overweight/obese diabetic patients of this study, this corroborating with the literature. We found certain DNA variations that could explain the hyperglycemic phenotype of the patients.

Vitamin D supplementation combined with aerobic physical exercise restores the cell density in hypothalamic nuclei of rats exposed to monosodium glutamate.

BACKGROUND & AIMS: In view of the increase in the prevalence of obesity and metabolic syndrome in childhood and adolescence, this study proposed the early and combined use of treatments to restore brain areas related to satiety. The vitamin D supplementation, aerobic exercise and the combination of these interventions on the structure of arcuate (ARC) and ventromedial (VMH) nuclei of hypothalamus were investigated in monosodium glutamate (MSG)-treated rats. METHODS: Wistar rats were separated into five groups: Control group (CT); Obese group injected with MSG (OB); Obese group supplemented with vitamin D (OBvd); Obese group submitted to forced swimming training (OBexe) and Obese group treated with vitamin D supplementation and forced swimming training (OBvd + exe). RESULTS: In the OB group, the visceral fat weight was significantly higher, there was a reduction in the number of glial cells in the ARC nucleus and also in the number of neurons in the ARC and VMH nuclei. Aerobic exercise was able to reduce the visceral fat weight in the OBexe group. The combination of treatments used in the OBvd + exe group reversed the loss of neurons and glial cells produced by MSG in the ARC nucleus. All treated groups exhibited a higher number of neurons in VMH nucleus, but an increase in the glial cells were observed only in the OBexe and OBvd + exe groups. CONCLUSIONS: The effectiveness of obesity treatment can be favored through the early and combined use of vitamin D supplementation and aerobic exercise, since these therapies are able to restore brain nuclei involved in the control of food intake.

Sex differences in brain cholinergic activity in MSG-obese rats submitted to exercise.

Obesity is an epidemic disease most commonly caused by a combination of increased energy intake and lack of physical activity. The cholinergic system has been shown to be involved in the regulation of food intake and energy expenditure. Moreover, physical exercise promotes a reduction of fat pads and body mass by increasing energy expenditure, but also influences the cholinergic system. The aim of this study is to evaluate the interaction between physical exercise (swimming) and central cholinergic activity in rats treated with monosodium glutamate (MSG, a model for obesity) during infancy. Our results show that MSG treatment is able to induce obesity in male and female rats. Specifically, MSG-treated rats presented a reduced body mass and nasoanal length, and increased perigonadal and retroperitoneal fat pads in relation to the body mass. Physical exercise was able to reduce body mass in both male and female rats, but did not change the fat pads in MSG-treated rats. Increased food intake was only seen in MSG-treated females submitted to exercise. Cholinergic activity was increased in the cortex of MSG-treated females and physical exercise was able to reduce this activity. Thalamic cholinergic activity was higher in sedentary MSG-treated females and exercised MSG-treated males. Hypothalamic cholinergic activity was higher in male and female MSG-treated rats, and was not reduced by exercise in the 2 sexes. Taken together, these results show that MSG treatment and physical exercise have different effects in the cholinergic activity of males and females.

Low-Intensity swimming training after weaning improves glucose and lipid homeostasis in MSG hypothalamic obese mice.

Low-intensity swimming training, started at an early age, was undertaken to observe glycemic control in hypothalamic obese mice produced by neonatal monosodium l-glutamate (MSG) treatment. Although swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, this event was not observed when exercise training is applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Current work verifies whether, besides reducing fat tissue accumulation, low-intensity swimming in MSG-weaned mice also improves glycemic control. Although MSG and control mice swam for 15 min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Retroperitonial fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Mice were also submitted to ipGTT. MSG obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance and insulin resistance. However, the exercise was able to block MSG treatment effects. Higher total cholesterol and triglycerides observed in MSG mice were normalized by exercise after weaning. Exercised MSG animals had higher HDLc than the sedentary group. Data suggest that early exercise training maintains normoglycemia, insulin tissue sensitivity, and normal lipid profile in mice programmed to develop metabolic syndrome.