RESUMEN
BACKGROUND: Leptin plays an important role in the regulation of the immune response. There is a physiological surge of leptin in rodents during the neonatal period, which has mainly been studied in the context of brain development. However, little is known about the effects of this neonatal leptin surge on immunity. Therefore, we investigated whether blocking this leptin surge could affect several immune functions. METHODS: Male and female rats were injected subcutaneously with 5 mg/Kg/day of rat pegylated super leptin antagonist during the neonatal period (PND5-9). On the peripubertal period, relevant functions as well as cytokine release by spleen leukocytes were studied in these animals. RESULTS: The results showed that the animals significantly display an impaired anti-tumor NK activity and chemotactic and proliferation capacity of lymphocytes in response to mitogens. In addition, several cytokine concentrations, released under mitogen-stimulated conditions, were also altered. CONCLUSION: In conclusion, the neonatal leptin surge seems to be involved in the establishment of an adequate immune response and cytokine profile, which are crucial for the maintenance of a healthy life.
Asunto(s)
Crecimiento y Desarrollo , Leptina , Animales , Animales Recién Nacidos/crecimiento & desarrollo , Animales Recién Nacidos/inmunología , Citocinas/análisis , Citocinas/inmunología , Femenino , Crecimiento y Desarrollo/inmunología , Inmunidad/inmunología , Inmunidad/fisiología , Péptidos y Proteínas de Señalización Intercelular/inmunología , Leptina/inmunología , Masculino , Ratas/inmunologíaRESUMEN
The aim of the present study was to investigate whether the late onset of diet-induced obesity (DIO) in middle-aged mice affected behavioral, immunological and oxidative stress parameters as well as life span of male and female mice. Also, it was analyzed whether the late DIO onset aggravated immunosenescence in old female mice. Late-adult male and female ICR/CD1 mice (28â¯weeks old) were fed either a high-fat diet or a standard diet during 14â¯weeks. After that, in these middle-aged (42â¯weeks old) diet-induced obese (DIO) and non-DIO controls, behavior as well as functions and redox state of peritoneal leukocytes were evaluated. These same parameters (excepting behavioral tests) were repeated when female mice were old (72â¯weeks old). The results showed lower exploratory activity and higher anxiety-like behavior in middle-aged male and female DIO than in controls. Moreover, these DIO animals from both sexes exhibited statistically significant impaired immune cell functions, such as chemotaxis of macrophages and lymphocytes, phagocytosis of macrophages, natural killer activity and lymphoproliferation in response to ConA and LPS, as well as an oxidative stress state in comparison with controls. Male DIO mice exhibited higher impairments in a variety of the evaluated parameters and a shorter life span than their female counterparts. In addition, female DIO mice, at old age, showed aggravated immunosenescence. In conclusion, the late DIO onset leads to impairments in behavior as well as in immune system functions of middle-aged male and female mice, males being significantly more affected than females.
Asunto(s)
Factores de Edad , Obesidad/inmunología , Obesidad/fisiopatología , Animales , Ansiedad/metabolismo , Conducta Animal/fisiología , Dieta Alta en Grasa/efectos adversos , Conducta Exploratoria/fisiología , Femenino , Leucocitos , Longevidad , Linfocitos , Macrófagos , Masculino , Ratones , Ratones Endogámicos ICR , Ratones Obesos , Oxidación-Reducción , Estrés Oxidativo/fisiología , Factores SexualesRESUMEN
The homeostatic systems, such as the nervous and immune systems, show deterioration in aging as a consequence of the age-related oxidative-inflammatory stress establishment. The supplementation with fermented milk containing probiotic bacteria could be a good nutritional strategy to improve homeostatic system functions in aged individuals through the modulation of their redox state. The aim of the present study was to evaluate the effect of 2-week supplementation with a commercial fermented milk containing yogurt species (Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus), and the probiotic Lactobacillus casei DN-114001 on behavior, redox state, and immune cell functions of aged mice as well as on their life span. Aged female ICR-CD1 mice were supplemented with fermented milk containing these probiotics for 2 weeks. After this period, a variety of behavioral tests were performed and several parameters of redox state and function of peritoneal leukocytes were analyzed. The results showed that the 2-week supplementation of fermented milk containing probiotics improved behavior (such as muscular vigor, exploratory activity, and anxiety-like behavior) as well as the redox state and functions of peritoneal immune cells in aged mice. In conclusion, the present study shows that the supplementation with fermented milk containing probiotics for a short period of time could be a good nutritional strategy to promote healthy aging.
Asunto(s)
Envejecimiento/inmunología , Envejecimiento/psicología , Sistema Inmunológico/efectos de los fármacos , Probióticos/administración & dosificación , Yogur/microbiología , Envejecimiento/efectos de los fármacos , Envejecimiento/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Femenino , Humanos , Sistema Inmunológico/inmunología , Lacticaseibacillus casei/fisiología , Lactobacillus delbrueckii/fisiología , Ratones , Ratones Endogámicos ICR , Oxidación-Reducción/efectos de los fármacos , Streptococcus thermophilus/fisiología , Yogur/análisisRESUMEN
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.
Asunto(s)
Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Enfermedades del Sistema Inmune/prevención & control , Sistema Inmunológico/fisiopatología , Obesidad/dietoterapia , Ácidos Oléicos/uso terapéutico , Estrés Oxidativo , Animales , Proliferación Celular , Células Cultivadas , Quimiotaxis de Leucocito , Dieta Alta en Grasa/efectos adversos , Femenino , Enfermedades del Sistema Inmune/etiología , Factores Inmunológicos/uso terapéutico , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/patología , Leucocitos/inmunología , Leucocitos/patología , Peroxidación de Lípido , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Macrófagos Peritoneales/patología , Ratones Endogámicos ICR , Mitógenos/farmacología , Obesidad/etiología , Obesidad/patología , Obesidad/fisiopatología , Fagocitosis/efectos de los fármacos , Análisis de SupervivenciaRESUMEN
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.
Asunto(s)
Inmunosenescencia/efectos de los fármacos , Obesidad/tratamiento farmacológico , Ácidos Oléicos/farmacología , Estrés Oxidativo/efectos de los fármacos , Bazo/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ácidos Grasos Omega-3 , Femenino , Glutatión/metabolismo , Disulfuro de Glutatión/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Linfocitos/efectos de los fármacos , Linfocitos/metabolismo , Ratones , Ratones Endogámicos ICR , Ratones Obesos , Obesidad/metabolismo , Bazo/metabolismoRESUMEN
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.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Ácidos Grasos Omega-3/uso terapéutico , Ácidos Oléicos/uso terapéutico , Animales , Femenino , Ratones , Ratones Obesos , Estrés Oxidativo/efectos de los fármacosRESUMEN
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.
Asunto(s)
Inflamación/metabolismo , Inflamación/patología , Leptina/antagonistas & inhibidores , Maduración Sexual , Tejido Adiposo Blanco/metabolismo , Animales , Animales Recién Nacidos , Peso Corporal , Catalasa/metabolismo , Citocinas/metabolismo , Femenino , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Hipotálamo/metabolismo , Masculino , Tamaño de los Órganos , Oxidación-Reducción , Estrés Oxidativo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Obesity and aging share an impaired immune system and oxidative and inflammatory stress. Therefore, the hypothesis of obesity as a possible model of premature immunosenescence has been proposed. In this study, we investigated whether adult obese mice, as a consequence of being fed with a fat-rich diet during their adolescence, showed premature immunosenescence and if this was aggravated with aging. Peritoneal cell suspensions were obtained when ICR/CD1 obese female mice were adults (28 weeks) and old (72 weeks), and several functions and antioxidant defenses were evaluated. The results showed that the chemotaxis of both macrophages and lymphocytes, phagocytosis of macrophages, activity of natural killer cells, proliferative response of lymphocytes, interleukin-1ß, tumor necrosis factor-alpha, interleukin-6, interleukin-2, and interleukin-10 released in leukocyte cultures, as well as antioxidant and oxidant capacity were significantly impaired in adult obese mice with respect to adult nonobese mice, with values similar to those in chronologically old mice. When these obese animals grew older, although having been fed with a standard diet, they showed a higher deterioration of their immune functions in comparison with the old control group. In conclusion, these results demonstrate that a high fat intake during adolescence can produce an obesity state in adult age associated with a premature immunosenescence, which is aggravated through aging.