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.

We evaluated the effect of exercise and vitamin D supplementation on histological aspects of the spleens of lean and obese rats. Male Wistar rats received neonatal administration of monosodium glutamate (MSG; 4g/Kg), while Control (CON) rats received an equimolar solution. At 30 days of age, CON and MSG rats were subdivided into Exercised (E) or Sedentary (S) groups and Vitamin D (VD; 12µg/Kg) supplemented or non-supplemented (NS) groups. At the 86th day of life, rats were euthanized, and their body weights and adiposity were evaluated. Spleens were submitted to histomorphometric analysis of the white pulp (WP), germinal center (GC) and lymphatic nodule (LN). Data are presented as mean ± SEM (p<0.05). MSG treatment promoted a reduction in spleen weight, increased LN thickness and WP area, but reduced GC occupation, compared to spleens of CON-lean rats (p<0.05). Exercise and VD did not provoke changes in the spleens of MSG-obese rats. In CON-lean rats, E and VD induced augmentation of LN thickness. VD supplementation increased the WP area, while E reduced GC area occupation in spleens of CON-lean rats (p<0.05). In conclusion, exercise and VD supplementation increased LN thickness and WP area, but had the opposite effect on the GC in spleens of CON-lean rats. However, neither exercise nor VD supplementation prevented the development of morphological abnormalities in the spleens of MSG-obese rats.

No abstract

The vagus nerve (VN) and spleen represent a complex interface between neural and immunological functions, affecting both energy metabolism and white adipose tissue (WAT) content. Here, we evaluated whether vagal and splenic axis participates in WAT mass regulation in obese and non-obese male Wistar rats. High doses of monosodium glutamate (M; 4 g/Kg) were administered during the neonatal period to induce hypothalamic lesion and obesity (M-Obese rats). Non-obese or Control (CTL) rats received equimolar saline. At 60 days of life, M-Obese and CTL rats were randomly distributed into experimental subgroups according to the following surgical procedures: sham, subdiaphragmatic vagotomy (SV), splenectomy (SPL), and SV + SPL (n = 11 rats/group). At 150 days of life and after 12 h of fasting, rats were euthanized, blood was collected, and the plasma levels of glucose, triglycerides, cholesterol, insulin, and interleukin 10 (IL10) were analyzed. The visceral and subcutaneous WAT depots were excised, weighed, and histologically evaluated for number and size of adipocytes as well as IL10 protein expression. M-Obese rats showed higher adiposity, hyperinsulinemia, hypertriglyceridemia, and insulin resistance when compared with CTL groups (p &lt; 0.05). In CTL and M-Obese rats, SV reduced body weight gain and triglycerides levels, diminishing adipocyte size without changes in IL10 expression in WAT (p&lt; 0.05). The SV procedure resulted in high IL10 plasma levels in CTL rats, but not in the M-Obese group. The splenectomy prevented the SV anti-adiposity effects, as well as blocked the elevation of IL10 levels in plasma of CTL rats. In contrast, neither SV nor SPL surgeries modified the plasma levels of IL10 and IL10 protein expression in WAT from M-Obese rats. In conclusion, vagotomy promotes body weight and adiposity reduction, elevating IL10 plasma levels in non-obese animals, in a spleen-dependent manner. Under hypothalamic obesity conditions, VN ablation also reduces body weight gain and adiposity, improving insulin sensitivity without changes in IL10 protein expression in WAT or IL10 plasma levels, in a spleen-independent manner. Our findings indicate that the vagal-spleen axis influence the WAT mass in a health state, while this mechanism seems to be disturbed in hypothalamic obese animals.

Objectives: This study aimed to evaluate the effect of vagotomy, when associated with splenectomy, on adiposity and glucose homeostasis in Wistar rats.Methods: Rats were divided into 4 groups: vagotomized (VAG), splenectomized (SPL), VAG + SPL, and SHAM. Glucose tolerance tests were performed, and physical and biochemical parameters evaluated. Glucose-induced insulin secretion and protein expression (Glut2/glucokinase) were measured in isolated pancreatic islets. Pancreases were submitted to histological and immunohistochemical analyses, and vagus nerve neural activity was recorded. Results:The vagotomized group presented with reduced body weight, growth, and adiposity; high food intake; reduced plasma glucose and triglyceride levels; and insulin resistance. The association of SPL with the VAG surgery attenuated, or abolished, the effects of VAG and reduced glucose-induced insulin secretion and interleukin-1β area in β cells, in addition to lowering vagal activity. Conclusions:The absence of the spleen attenuated or blocked the effects of VAG on adiposity, triglycerides and glucose homeostasis, suggesting a synergistic effect of both on metabolism. The vagus nerve and spleen modulate the presence of interleukin-1β in β cells, possibly because of the reduction of glucose-induced insulin secretion, indicating a bidirectional flow between autonomous neural firing and the spleen, with repercussions for the endocrine pancreas.

Maternal obesity induced by cafeteria diet (CAF) predisposes offspring to obesity and metabolic diseases, events that could be avoided by maternal bariatric surgery (BS). Herein we evaluated whether maternal BS is able to modulate brown adipose tissue (BAT) morphology and function in adult male rats born from obese female rats submitted to Roux-en-Y gastric bypass (RYGB). For this, adult male rat offspring were obtained from female rats that consumed standard diet (CTL), or CAF diet, and were submitted to simulated operation or RYGB. Analysis of offspring showed that, at 120 days of life, the maternal CAF diet induced adiposity and decreased the expression of mitochondrial Complex I (CI) and Complex III (CIII) in the BAT, resulting in higher accumulation of lipids than in BAT from offspring of CTL dams. Moreover, maternal RYGB increased UCP1 expression and prevented excessive deposition of lipids in the BAT of adult male offspring rats. However, maternal RYGB failed to reverse the effects of maternal diet on CI and CIII expression. Thus, maternal CAF promotes higher lipid deposition in the BAT of offspring, contributing to elevated adiposity. Maternal RYGB prevented obesity in offspring, probably by increasing the expression of UCP1.

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.

The present study aimed at evaluating histopathological changes in gills of Rhamdia quelenjuveniles submitted to different concentrations of ibuprofen (0.0; 0.5; 5.0 and 50.0 mg/L); concentrations were determined from LC50acute assays of 5.0mg/L(120h). For each concentration four replicates were made, with four copies each. The experiment had a total duration of 120 hours in a chronic toxicological trial. After completion, the animals were euthanized, laparotomized, and the gills were localized, isolated and fixed in 10% formaldehyde, preserved in 70% alcohol and subsequently submitted to histological routine technique for paraffin inclusion. Fivecuts (6μM) per specimen were made and stained with Hematoxylin and Eosin (H&E). The Average Alteration Score(AAS) and Histopathological Alteration Indices (HAI) were determined according to the degree of the lesion and then classified in stages I, II and III which produced respectively Lamellar derangement, Lamella’s epithelium rupture and aneurysm with more expressive alterations. For all concentrations the drug led to histological alterations for Rhamdia quelen, putting in evidence damages that go from moderate to severe in the gills of the analysed fishes. Ibuprofen caused branchial lesions in R.quelenwith a progressive effect in high concentrations, suggesting that the presence of this drug could cause abnormalities and favour mortality in this species.