Impacto da ausência do nervo vago e baço sobre o eixo hepcidina-ferro em ratos wistar machos submetidos à natação regular e sua repercussão sobre a massa adiposa

Abstract

. White adipose tissue (WAT) is a specialized territory for storing calories in the form of triglycerides and producing a set of paracrine and endocrine substances, called adipokines, which regulate hunger, satiety and the metabolism of carbohydrates and lipids. More recently, it has been demonstrated that WAT participates in the homeostasis of iron, a mineral essential to health, important for mitochondrial function and oxygen transport to tissues. The main regulator of systemic iron is the peptide hormone hepcidin, which modulates intestinal uptake and endogenous bioavailability of this mineral, and its secretion is influenced by Interleukin 6 (IL6). Iron in adipocytes regulates adipogenesis and insulin sensitivity, in close relationship with the immune system. In this context, the Vagus Nerve (VN) participates in the anti-inflammatory reflex, for which the presence of the spleen is essential and whose impact on iron homeostasis is unknown, especially during physical exercise. Objective: To evaluate the impact of the absence of the NV and spleen on the hepcidin-iron axis and its repercussions on adipose mass in male Wistar rats. Methods: At 60 days of age, male Wistar rats were randomly distributed into groups according to the surgical technique: spleen removal (splenectomy [SPL]), total NV section (bilateral subdiaphragmatic vagotomy [SV]), combination of SPL+SV or sham operation (SHAM). At 80 days, the groups were subdivided into sedentary (SD) and exercised (EX). Exercised rats swam 5 times a week/30 minutes for 8 weeks. Thus, 5 groups were formed: SHAM-SD; SHAM-EX; SPL-EX; SV-EX; SV+SPL- EX (n=6/group). At 120 days, the animals were euthanized, and whole blood was collected for analysis of glucose, triglycerides, cholesterol, and iron and hepcidin levels. The triglyceride and glucose index (TyG) was calculated. Inguinal (I-TAB) and retroperitoneal (R-TAB) WAT were collected for histological analysis of adipocyte number and area. Results: Exercise did not alter weight gain (p=0.1677), growth (p=0.0967), plasma glucose (p=0.7363) or triglyceride (p=0.9218) concentrations. However, the EX groups presented high levels of total cholesterol (Sham-Ex: p=0.0002; Spl-Ex: p=0.0057; Sv-Ex: p=0.0012; Sv+Spl-Ex: p= 0.0082). Plasma concentrations of iron and hepcidin were not altered by exercise (p=0.2089; p=0.0951), and there were no effects on the content of WAT-I. However, in the Sv-Ex (p=0.0394; p=0.0008; p=0.0013; p=0.0001) and Sv+Spl-Ex (p=0.0497; p<0.0001; p=0.0003; p=0.0001) groups, a reduction in the size and an increase in the number of adipocytes in the WAT-I depots were noted. TAB-R in relation to SHAM-SD. SHAM-SD rats showed a positive correlation between iron levels and tissue weight (p=0.0177) and adipocyte number (p=0.0044) of TAB-I. Conclusion: The data indicate that the absence of NV, especially with splenectomy, favors the reduction of subcutaneous and visceral WAT mass, decreasing the size of adipocytes in exercised rats. These effects are independent of the oscillation in circulating iron or hepcidin levels.