title: Oxidative stress and immunosenescence in spleen of obese mice can be reversed by 2-hydroxyoleic acid.
abstract: What is the central question of this study? Evidence is growing for the link between obesity, immune dysfunction and oxidative stress, but it is still not known how the properties and functions of the spleen and splenic leucocytes are affected. What is the main finding and its importance? Obesity led to premature immunosenescence, manifested as oxidative stress and changes in leucocyte functions in mouse spleen. The oleic acid derivative 2-hydroxyoleate and, to a lesser extent, a combination of eicosapentaenoic and docosahexaenoic acids could reverse most of the observed alterations, suggesting a potential therapeutic tool for obesity-related immune dysfunction and redox imbalance. We aimed to investigate the effects of obesity on oxidative stress and leucocyte function in the mouse spleen and to assess whether supplementation with 2-hydroxyoleic acid (2-OHOA) or n-3 polyunsaturated fatty acids (PUFAs) 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 divided into the following three groups (n = 8 per group): no supplementation; 2-OHOA supplementation (1500 mg kg-1of diet); and n-3 PUFA supplementation (eicosapentaenoic acid and docosahexaenoic acid, 1500 + 1500 mg kg-1of diet). Eight mice were fed the 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 glutathione (GSSG), GSH/GSSG, xanthine oxidase activity, lipid peroxidation, lymphocyte chemotaxis, natural killer activity and mitogen (concanavalin A and lipopolysaccharide)-induced lymphocyte proliferation. Obese animals presented higher GSSG levels (P = 0.003), GSSG/GSH ratio (P = 0.013), lipid peroxidation (P = 0.004), xanthine oxidase activity (P = 0.015) and lymphocyte chemotaxis (P < 0.001), and lower natural killer activity (P = 0.003) and proliferation in response to concanavalin A (P < 0.001) than control mice. 2-Hydroxyoleic acid totally or partly reversed most of the changes (body weight, fat content, GSSG levels, GSH/GSSG, lipid peroxidation, chemotaxis and proliferation, all P < 0.05), whereas n-3 PUFAs reversed the increase in xanthine oxidase activity (P = 0.032). In conclusion, 2-OHOA or, to a lesser extent, n-3 PUFAs could ameliorate the oxidative stress and alteration of leucocyte function in the spleens of obese mice. Our findings support a link between obesity and immunosenescence and suggest a potential therapeutic tool for obesity-related immune dysfunction.
authors.affiliation: Immunonutrition Research Group, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Madrid, Spain.
authors.forename: Alina
authors.initials: A
authors.lastname: Gheorghe
authors.affiliation: School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool, UK.
authors.forename: Fátima
authors.identifier: 0000-0002-2537-3327
authors.initials: F
authors.lastname: Pérez de Heredia
authors.affiliation: Department of Animal Physiology II, Faculty of Biology, University Complutense of Madrid, Madrid, Spain.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hunsche
authors.affiliation: Immunonutrition Research Group, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Madrid, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Redondo
authors.affiliation: Immunonutrition Research Group, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Madrid, Spain.
authors.forename: Ligia Esperanza
authors.initials: LE
authors.lastname: Díaz
authors.affiliation: Department of Animal Physiology II, Faculty of Biology, University Complutense of Madrid, Madrid, Spain.
authors.forename: Oskarina
authors.initials: O
authors.lastname: Hernández
authors.affiliation: Immunonutrition Research Group, Institute of Food Science, Technology and Nutrition (ICTAN), Spanish National Research Council (CSIC), Madrid, Spain.
authors.forename: Ascensión
authors.initials: A
authors.lastname: Marcos
authors.affiliation: Department of Animal Physiology II, Faculty of Biology, University Complutense of Madrid, Madrid, Spain.|Research Institute of the Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: De la Fuente
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015525:Fatty Acids, Omega-3; D005260:Female; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D000068884:Immunosenescence / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008820:Mice, Obese; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D009829:Oleic Acids / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D013154:Spleen / Q000187:drug effects* / Q000378:metabolism
chemical_list: C483229:2-hydroxyoleic acid; D015525:Fatty Acids, Omega-3; D009829:Oleic Acids; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: Oxidative stress; immunosenescence; obesity