Involvement of Nuclear Related Factor 2 Signaling Pathway in the Brain of Obese Rats and Obesity-Resistant Rats Induced by High-Fat Diet.

Abstract

We aimed to investigate the mechanism of brain damage in diet-induced obese (DIO) rats and diet-resistant (DR) rats from the viewpoint of redox state and nuclear related factor 2 (Nrf2) signaling pathway. Sprague-Dawley rats were fed with a high-fat diet for 10 weeks to obtain the DIO and DR rats. d-Galactose was injected subcutaneously through the back of the neck for 10 weeks to establish oxidative stress model rats. Then, the ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and the level of glutathione peroxidase (GSH-Px) in serum and brain tissue were measured by using enzymatic assay kits. The levels of cholecystokinin and peptide YY in the brain tissue were detected by using enzyme-linked immunosorbent assay kits. In addition, the protein expression of Nrf2 and its downstream factors such as heme oxygenase 1, manganese superoxide dismutase, and NAD(P)H quinone oxidoreductase 1 (NQO1) in the brain tissue were measured by Western blotting. In the brain of DIO rats, the level of GSH and ratio of GSH/GSSG were lower, whereas the GSH-Px concentration was higher compared with DR rats significantly. On the other hand, the GSSG level was higher in the serum of DIO rats compared with the DR rats. The oxidative stress state in the brain of DIO rats, but not in DR rats, were observed. In addition, the protein expressions of Nrf2 and NQO1 were downregulated in the brain of DR rats compared with that in DIO rats. Our data suggest that the Nrf2/NQO1 signaling pathway and redox state were involved in the pathogenesis of the rats prone to obesity, but not the DR rats resistant to obesity.