O nervo vago influencia o eixo hepcidina-ferro e a histologia do tecido esplênico em ratos Wistar obesos e não obesos induzidos à anemia hemolítica.

Abstract

Introduction: The spleen plays a central role in immune responses and iron recycling through the reticuloendothelial system. Obesity exerts deleterious effects on splenic metabolic and immune activities, as well as on the regulation of endogenous iron, thereby favoring the development of anemia. In this context, the low-grade chronic inflammation characteristic of obesity has been associated with disruption of iron homeostasis, a process that appears to involve alterations in the secretion of hepcidin, the principal hormone regulating systemic iron flow. The parasympathetic branch of the autonomic nervous system, via Vagus Nerve (VN), exerts an anti-inflammatory effect that depends on splenic activity. However, whether this VN-spleen interface modulates iron homeostasis remains unclear. Objective: To evaluate the effects of VN absence on the splenic histology of obese and non-obese rodents induced to hemolytic anemia by phenylhydrazine. Methods: Male Wistar rats were rendered obese through hypothalamic injury induced by subcutaneous administration of monosodium glutamate (MSG; 4 g/kg) from postnatal day 2 to 10 (PND 2–10). Control rats (CTRL) received an equimolar saline solution. On PND 60, MSG (n=32) and CTRL (n=32) rats were randomly assigned into subgroups (n=16) according to the surgical procedures: subdiaphragmatic vagotomy (SV) or sham operation (SHAM). On PND 90, half of the animals in each group (n=8) were induced to hemolytic anemia by intraperitoneal administration of phenylhydrazine (PHZ; 40 mg/kg). On PND 120, animals were weighed and euthanized; whole blood was collected for plasma analysis, including iron and hepcidin quantification. Retroperitoneal white adipose tissue (rWAT) was excised and weighed. The spleen was harvested, weighed, and stored for histological analysis to assess area and morphological aspects of the White Pulp (WP), including the Lymphoid Nodule (LN) and Marginal Zone (MZ), as well as Red Pulp (RP) area. Results: MSG-treated animals developed obesity, associated with hypertriglyceridemia, insulin resistance (IR), and decreased circulating iron and hepcidin concentrations, along with reduced spleen weight, decreased WP and RP areas, and increased iron deposition compared to CTRL rats. In both CTRL and MSG groups, SV reduced body weight and adiposity and increased stomach weight. In the CTRLSV group, worsened TG and IR were observed, accompanied by reduced plasma hepcidin levels and increased hemosiderin deposits in splenic tissue. In CTRLPHZ animals, spleen weight was increased, with no significant histological changes, except for a reduced number of WP per field due to PHZ. However, in MSGSV animals, TG levels decreased, IR and fasting glycemia improved, and plasma hepcidin concentration increased – an effect enhanced in the MSGSV+PHZ group. The area and number of WP per field were greater in the MSGSV group. MSGPHZ rats exhibited splenomegaly and increased hemosiderin deposition, with a reduction in LN area and an increase in RP area. Conclusion: Rats with hypothalamic obesity present alterations in the hepcidin-iron axis, with greater splenic iron accumulation. The absence of vagal signaling increases iron deposition in splenic tissue and exerts opposite effects on hepcidin concentration in healthy and obese rats.