Oxidative stress and immunosenescence in spleen of obese mice can be reversed by 2-hydroxyoleic acid.

Abstract

We aimed to investigate the effects of obesity on oxidative stress and leukocyte function in spleen of mice, and to assess whether supplementation with 2-hydroxyoleic acid (2-OHOA) or n-3 polyunsaturated fatty acids (PUFA) could reverse those effects. Female ICR/CD1 mice (8 weeks old, n = 24) received an obesogenic diet (22% fat for 4 weeks and 60% fat for 14 weeks). After 6 weeks, mice were split in three groups (n = 8/group): no supplementation, 2-OHOA supplementation (1500 mg kg(-1) ) and n-3 PUFA supplementation (EPA + DHA, 3000 mg kg(-1) diet). Eight mice were fed standard diet for the whole duration of the study (control group). At the end of the experiment, the following variables were assessed in spleens: levels of reduced (GSH) and oxidized (GSSG) glutathione, GSH/GSSG, xanthine oxidase (XO) activity, lipid peroxidation, lymphocyte chemotaxis, natural killer (NK) activity and mitogen (ConA and LPS)-induced lymphocyte proliferation. Obese animals presented higher GSSG levels (P = 0.003), GSSG/GSH ratio (P = 0.013), lipid peroxidation (P = 0.004), XO activity (P = 0.015) and lymphocyte chemotaxis (P < 0.001), and lower NK activity (P = 0.003) and proliferation in response to ConA (P < 0.001) than controls. 2-OHOA reversed totally or partially most of the changes (body weight, fat content, GSSG levels, GSH/GSSG, lipid peroxidation, chemotaxis and proliferation, all P < 0.05), while n-3 PUFA reversed the increase in XO activity (P = 0.032). In conclusion, 2-OHOA, and to a lesser extent n-3 PUFA, could ameliorate the oxidative stress and alteration of leukocyte function in spleen of obese mice. Our findings support a link between obesity and immunosenescence and suggest a potential therapeutic tool for obesity-related immune dysfunction. This article is protected by copyright. All rights reserved