Vagal Splenic‐Dependent Effects Influence Glucose Homeostasis, Insulin Secretion, and Histopathology of the Endocrine Pancreas in Hypothalamic Obese Male Rats

Vagus nerve (VN) and spleen dysfunctions are often associated with obesity (Ob). <b>Aim:</b> We evaluated the effects of VN and spleen ablation on adiposity, metabolism, and insulin secretion in hypothalamic obese male rats. <b>Methods:</b> Ob was induced by neonatal subcutaneous injection of monosodium glutamate (4 g/kg). At 60 days of life, Ob animals were randomly distributed into four groups (<i>n</i> = 16 rats/group): sham operation (SHAM), vagotomy (VAG), splenectomy (SPL), and VAG + SPL. Body weight and food intake were monitored for 8 weeks postsurgery. Intraperitoneal glucose tolerance test (ipGTT) and intraperitoneal pyruvate tolerance test (ipPTT) were performed at 148 days of life, and VN activity was recorded at 150 days. After euthanasia (150 days), adiposity, plasma biochemical parameters, glucose-induced insulin secretion (GIIS), and cholinergic and adrenergic islet responsiveness were evaluated. The pancreas was submitted for histopathological analysis, and the protein content of OXPHOS and IL-10 was evaluated in isolated pancreatic islets. <b>Results:</b> Decreased VN activity was confirmed in the Ob-VAG groups, associated with lower visceral adiposity, triglycerides, and plasma insulin, together with improved insulin sensibility and pyruvate tolerance, compared to Ob-SHAM rats. Spleen absence reduced VN activity and cholinergic insulinotropic responses, with deleterious effects on the endocrine pancreas. Furthermore, Ob-VAG + SPL rats presented greater reductions in GIIS and more severe endocrine pancreas histopathology, compared to the Ob-SHAM group, without altered islet size or number or protein content of OXPHOS or IL-10. <b>Conclusion:</b> Vagal and splenic interactions contribute to glucose homeostasis control in hypothalamic obese rats, modulating insulin secretion and pancreas histology.