The supplementations with 2-hydroxyoleic acid and n-3 polyunsaturated fatty acids revert oxidative stress in various organs of diet-induced obese mice.

Obesity and its related diseases have been associated with oxidative stress. Thus, the search for nutritional strategies to ameliorate oxidative stress in obese individuals seems important. We hypothesized that the supplementation with monounsaturated (2-hydroxyoleic acid (2-OHOA)) and with combined n-3 polyunsaturated (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) fatty acids would ameliorate oxidative stress in different organs, including brain, liver, lungs, and kidneys of adult diet-induced obese (DIO) mice. Adult female ICR-CD1 mice were fed a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of DIO mice received the same HFD, supplemented with 1500 mg of 2-OHOA per kg of HFD and another group with 1500 mg of EPA and 1500 mg of DHA per kg of HFD. At the end of the experiment, several parameters of oxidative stress were assessed. The supplementation with 2-OHOA or with EPA and DHA in DIO mice was able to revert oxidative stress, enhancing the activities of catalase and glutathione reductase, as well as diminishing the activity of xanthine oxidase, the concentration of thiobarbituric acid reactive substances (TBARS) and the ratio between oxidized glutathione and reduced glutathione in several organs. These reached similar values to those of control mice, which were fed a standard diet. These data suggest that supplementation with 2-OHOA and with EPA and DHA could be an effective nutritional intervention to restore an appropriate redox state in DIO mice.

Immune dysfunction and increased oxidative stress state in diet-induced obese mice are reverted by nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids.

PURPOSE: Obesity is associated with impaired immune defences and chronic low levels of inflammation and oxidation. In addition, this condition may lead to premature aging. The aim of the study was to evaluate the effects of a nutritional supplementation with monounsaturated and n-3 polyunsaturated fatty acids on several functions and oxidative stress parameters in peritoneal immune cells of obese mice, as well as on the life span of these animals. METHODS: Obesity was induced in adult female ICR/CD1 by the administration of a high-fat diet (HFD) for 14 weeks. During the last 6 weeks of HFD feeding, one group of obese mice received the same HFD, supplemented with 1500 mg of 2-hydroxyoleic acid (2-OHOA) and another with 3000 mg of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Several functions and oxidative stress parameters of peritoneal leukocytes were evaluated. RESULTS: The groups of obese mice treated with 2-OHOA or with EPA and DHA showed a significant improvement in several functions such as chemotaxis, phagocytosis, digestion capacity, Natural killer activity and lymphoproliferation in response to mitogens. All of these functions, which were decreased in obese mice, increased reaching similar levels to those found in non-obese controls. Both treatments also improved oxidative stress parameters such as xanthine oxidase activity, which decreased, catalase activity and glutathione levels, which increased. CONCLUSION: These data suggest that dietary supplementation with monounsaturated and n-3 polyunsaturated fatty acids could be an effective nutritional intervention to restore the immune response and oxidative stress state, which are impaired in obese mice.

Administration of a leptin antagonist during the neonatal leptin surge induces alterations in the redox and inflammatory state in peripubertal /adolescent rats.

The importance of the neonatal leptin surge in rodents in neurodevelopmental processes has aroused curiosity in its implication in other physiological systems. Given the role of leptin in neuro-immune interactions, we hypothesized that the neonatal leptin surge could have an effect on the oxidative and inflammatory stress situations of both systems. We blocked the neonatal leptin surge by a leptin antagonist and measured several parameters of oxidative and inflammatory stress in the spleen, hypothalamus and adipose tissue of peripubertal/adolescent rats. The treated rats showed lower activity of several antioxidant enzymes in the spleen and their leukocytes released lower levels of mitogen-stimulated IL-10 and IL-13 and higher levels of TNF-alpha. In conclusion, the neonatal leptin surge may have a key role in the establishment of adequate redox and inflammatory states in the immune system, which is important for the generation of adequate immune responses and to obtain and maintain good health.

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

NEW FINDINGS: 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-1 of diet); and n-3 PUFA supplementation (eicosapentaenoic acid and docosahexaenoic acid, 1500 + 1500 mg kg-1 of 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.