Chemotherapy delays progression of motor neuron disease in the SOD1 G93A transgenic mouse.

The vagus nerve (VN) and spleen are involved in the anti-inflammatory vagal reflex, which influences the metabolic state, with unknown effects on iron metabolism. Here, we evaluate the impact of subdiaphragmatic vagotomy (SV) and splenectomy (SPL) on iron homeostasis in lean and hypothalamic obese male rats after haemolytic anaemia induction. Hypothalamic obesity was induced by monosodium glutamate (MSG; 4 g/kg), administered subcutaneously (s.c.) once every other day from post-natal day 2 (PND2) to PND10. Lean or control (CTRL) rats received equimolar saline (1.25 g/kg; s.c.). On PND60, rats underwent SV, SPL, SV + SPL, or SHAM surgeries. At PND90, haemolytic anaemia was induced by intraperitoneal phenylhydrazine (PHZ; 40 mg/kg). At PND120, the rats were evaluated for adiposity and metabolism, and plasma samples were used to measure iron, hepcidin, total iron-binding capacity (TIBC), and transferrin saturation (TSAT). MSG-obese rats exhibited normal amounts of iron and hepcidin (P > 0.05), associated with increased values of TIBC and TSAT (P < 0.05), compared with CTRL rats. SV reduced adiposity in both CTRL and MSG-obese rats without altering iron levels. However, in MSG-obese animals only, the anti-adiposity effects of SV were accompanied by positive effects on metabolism, especially in association with SPL and PHZ (P < 0.05). SV increased TSAT in MSG-obese animals (P < 0.05). PHZ-induced haemolytic anaemia increased the circulating levels of hepcidin (P < 0.05) in MSG-obese rats, with this response being influenced by the VN and spleen. In conclusion, vagal and splenic mechanisms regulate the adiposity and metabolism of MSG-hypothalamic obese rats, modulating hepcidin and iron transport capacity, independently of fluctuations in plasma iron levels.