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.

Splenic participation in glycemic homeostasis in obese and non-obese male rats.

We evaluated the effects of splenectomy on glucose homeostasis in obese and non-obese rats. Obesity was induced by subcutaneous injections of monosodium glutamate (MSG; 4g/kg) in neonatal rats. Control (non-obese) animals received equimolar saline. Splenectomy (SPL) was performed at 21 or 60 days of life (SPL21 and SPL60) in MSG obese and non-obese groups. Glucose tolerance, insulin resistance (IR), adiposity, histology of white adipose tissue (WAT) depots and glucose-induced insulin secretion (GIIS) in isolated pancreatic islets were evaluated at 90 days of life. In non-obese, despite of hyperphagia, the spleen ablation reduced body weight gain and energy efficiency, without changes in GIIS or IR. Slight reduction in glucose tolerance and augmented adipocyte size in subcutaneous WAT was noted in non-obese SPL21 group. In MSG-SPL21 rats was observed augmented body weight gain and energy efficiency, without alter adipocyte size. In contrast, MSG-SPL60 rats had lower body weight gain, reduced energy efficiency and smaller adipocyte size in WAT visceral depot in relation to MSG non-operated. Spleen ablation reduced insulin plasma levels in the MSG-SPL21 and MSG-SPL60 groups. Moreover, splenectomy reduced GIIS and improved glucose tolerance in MSG-SPL21 group. In MSG-SPL60 rats were observed reduction in IR, without changes in GIIS, despite of elevated glucokinase expression in pancreatic islets. In conclusion, spleen ablation reduces body weight in non-obese rats and slightly modifies glucose homeostasis. In contrast, in MSG-induced obesity, absence of the spleen can ameliorate glucose tolerance and reduce insulin secretion, improving insulin sensitivity.