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.

The Vagus Nerve and Spleen: Influence on White Adipose Mass and Histology of Obese and Non-obese Rats.

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 < 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< 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.

Vagotomy and Splenectomy Reduce Insulin Secretion and Interleukin-1ß.

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-1ß area in ß 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-1ß in ß 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 Roux-en-Y gastric bypass surgery reduces lipid deposition and increases UCP1 expression in the brown adipose tissue of male offspring.

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.

DUODENAL-JEJUNAL BYPASS REDUCES LIPID ACCUMULATION IN THE BROWN ADIPOSE TISSUE OF HYPOTHALAMIC OBESE RATS.

BACKGROUND: Effects of duodenal-jejunal bypass surgery (DJB) on the proliferation of nuclei and the area of adipocytes in the brown adipose tissue of obese rats. Thermogenic activity in the brown adipose tissue (BAT) of obese individuals is reduced, and this condition may be modified by bariatric surgery (BS). AIM: To characterize fat deposition in BAT from hypothalamic obese (HyO) rats submitted to duodenal-jejunal-bypass (DJB) surgery. METHODS: For induction of hypothalamic obesity, newborn male Wistar rats were treated with subcutaneous injections of monosodium glutamate (MSG). The control (CTL) group received saline solution. At 90 days, the HyO rats were submitted to DJB or sham operation, generating the HyO-DJB and HyO-SHAM groups. At 270 days, the rats were euthanized, and the BAT was weighed and submitted to histological analysis. RESULTS: Compared to BAT from CTL animals, the BAT from HyO-SHAM rats displayed increased weight, hypertrophy with greater lipid accumulation and a reduction in nucleus number. DJB effectively increased nucleus number and normalized lipid deposition in the BAT of HyO-SHAM rats, similar to that observed in CTL animals. CONCLUSION: DJB surgery avoided excessive lipid deposition in the BAT of hypothalamic obese rats, suggesting that this procedure could reactivate thermogenesis in BAT, and contribute to increase energy expenditure.

Duodenal-jejunal bypass reduces lipid accumulation in the brown adipose tissue of hypothalamic obese rats / Derivação duodeno-jejunal reduz o acúmulo de lipídios no tecido adiposo marrom de ratos com obesidade hipotalâmica

ABSTRACT Background: Thermogenic activity in the brown adipose tissue (BAT) of obese individuals is reduced, and this condition may be modified by bariatric surgery (BS). Aim: To characterize fat deposition in BAT from hypothalamic obese (HyO) rats submitted to duodenal-jejunal-bypass (DJB) surgery. Methods: For induction of hypothalamic obesity, newborn male Wistar rats were treated with subcutaneous injections of monosodium glutamate (MSG). The control (CTL) group received saline solution. At 90 days, the HyO rats were submitted to DJB or sham operation, generating the HyO-DJB and HyO-SHAM groups. At 270 days, the rats were euthanized, and the BAT was weighed and submitted to histological analysis. Results: Compared to BAT from CTL animals, the BAT from HyO-SHAM rats displayed increased weight, hypertrophy with greater lipid accumulation and a reduction in nucleus number. DJB effectively increased nucleus number and normalized lipid deposition in the BAT of HyO-SHAM rats, similar to that observed in CTL animals. Conclusion: DJB surgery avoided excessive lipid deposition in the BAT of hypothalamic obese rats, suggesting that this procedure could reactivate thermogenesis in BAT, and contribute to increase energy expenditure.

RESUMO Racional: A atividade termogênica no tecido adiposo marrom (TAM) de indivíduos obesos encontra-se reduzida, condição que pode ser modificada pela cirurgia bariátrica(CB). Objetivo: Verificar o efeito da derivação duodeno-jejunal (DDJ) sobre a morfologia do TAM de ratos com obesidade hipotalâmica. Métodos: Para indução da obesidade hipotalâmica (OHi), ratos Wistar neonatos receberam injeções subcutâneas de glutamato monossódico (MSG). O grupo controle (CTL) recebeu solução salina. Aos 90 dias, os ratos OHi foram submetidos à DDJ (grupo OHi-DDJ) ou a falsa operação (grupo OHi-FO). Aos 270 dias, eles foram eutanasiados e o TAM foi pesado e submetido à análise histológica. Resultados: Em comparação com os animais CTL, o TAM dos ratos OHi-FO apresentou aumento do peso, hipertrofia dos adipócitos com acúmulo de lipídios e redução do número de núcleos. A DDJ reduziu a deposição de gordura e o número de núcleos no TAM de ratos OHi-DDJ em comparação com os OHi-FO, com valores similares aqueles dos animais CTL. Conclusões: A DDJ foi capaz de evitar a deposição excessiva de lipídios no TAM de ratos com obesidade hipotalâmica, sugerindo que a cirurgia bariátrica poderia reativar a termogênese neste tecido adiposo, contribuindo para aumentar o gasto energético.