Oscar Lamas

T-helper lymphopenia and decreased mitogenic response in cafeteria diet-induced obese rats

Obese individuals are more susceptible to infection than lean subjects. However, the underlying causes are not fully understood. To investigate whether obesity status influences immune response, we examined the immune function of diet-induced obese rats after 5 weeks of cafeteria feeding. Spleen lymphocyte subsets, blastogenic response to mitogens, phagocytosis, oxidative burst activity and the production of several cytokines by splenocytes were determined. Flow cytometric analysis revealed that spleen T helper cells were significantly reduced in obese rats without changes in T cytotoxic cells. Proliferative responses of splenocytes to LPS (lipopolysaccharide) and PHA (phytohaemagglutinin) from obese rats were significantly lower compared to their lean mates. Although no differences were found in phagocytic activity, a lower production of reactive oxygen metabolites (ROS) was noted in diet-induced obese animals as compared to lean rats. Finally, IL-2 production after mitogen addition was lower in cafeteria fed rats than in those receiving the control diet whereas IL-10 production tended to be higher in obese rats compared to lean animals. These results suggest that diet-induced obesity is accompanied by a reduction in the size of the T-helper pool, an impairment of splenocyte and monocyte responsiveness, decreased IL-2 and slightly increased IL-10 release by spleen, which may be related to potential health problems.

Decreased splenic mRNA expression levels of TNF-α and IL-6 in diet-induced obese animals

Obesity could be considered as a systemic low-grade inflammatory condition affecting inflammation markers. Adipose tissue synthesizes cytokines whose degree of elevation may depend on the obesity status. Recently, new information is collected on the cross-talking between immune system and adipose tissue in obesity. We report hereby that tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) gene expression in spleen of diet-induced obese animals were markedly decreased (more than 50%) as a consequence of the high fat feeding during five weeks. Interestingly, a very significant negative correlation was found between splenic TNF-α mRNA levels and total fat pads (r=−0.806, p=0.000). These findings support the hypothesis that TNF-α gene expression may follow different trends in obese animals adipocytes and splenocytes.ResumenLa obesidad ha sido recientemente considerada como un proceso inflamatorio sistémico de baja intensidad, que lleva asociado cambios en marcadores de inflamación. El tejido adiposo produce citoquinas cuyos niveles dependen de la acumulación de grasa corporal. Algunos datos revelan que existen moléculas señal que actúan tanto en el sistema inmunológico como en el tejido adiposo. En este trabajo se evalúa la expresión génica del TNF-α y IL-6 en el bazo de ratas obesas tras la alimentación con una dieta hipercalórica, observándose una disminución (superior al 50%) de los niveles de mRNA de ambas citoquinas al cabo de 5 semanas con ese régimen dietético. En cambio, los niveles de expresión de TNF-α se correlacionan negativa y muy significativamente con los depósitos grasos de los animales, lo cual sugiere que la expresión del gen del TNF-α varía según se trate de adipocitos o de esplenocitos.

Effects of a β3-adrenergic agonist on the immune response in diet-induced (cafeteria) obese animals

Molecules with affinity for β3-adrenoceptors are not only effective anti-obesity agents in rodent models, but may play a role in the regulation of the immune response. The aim of the current investigation was to analyse the effects of trecadrine on the immune response in diet-induced (cafeteria) obese rats. Male Wistar rats were divided into 2 groups, the control group (C, n=9) was fed with the standard pelleted chow laboratory diet, while the other group was fed with a high-fat (cafeteria) diet. Cafeteria-fed rats were divided into two new subgroups (n=9 each), which received either i.p. saline (obese, O) or trecadrine (1 mg/kg/day) (obese+trecadrine, O+T) daily for 5 weeks. Lymphocyte subpopulations and the proliferative response were determined by validated procedures. The administration of trecadrine was able to prevent the onset of obesity in cafeteria-fed rats. Trecadrine-treatment to obese animals appeared to improve the number of lymphocyte subpopulations (CD4+ and CD8+) as compared to those animals only receiving the high-fat diet, being the values of the trecadrine-treated animals on the high-fat diet similar to the control rats. However, the lymphoproliferative response when stimulated with several mitogens was markedly reduced by the cafeteria intake and was further decreased by the β3-adrenergic administration. The spleen mRNA expression level of UCP2, PPARγ and Ob-Rb were not affected by the trecadrine treatment. Summing up, at the immune system level, trecadrine administration increased the proportion of CD4+ spleen lymphocytes, although it was not able to restore the lymphocyte proliferative response which was depressed.ResumenEl agonista β3-adrenérgico trecadrine es un conocido agente anti-obesidad, cuya eficacia ha sido previamente comprobada en modelos animales. Además, es conocida la implicación de los agonistas adrenérgicos β en la regulación de la respuesta inmune. El objetivo del presente trabajo consiste en investigar el efecto del trecadrine sobre la respuesta inmune en animales con obesidad inducida por una dieta rica en grasa (dieta de cafetería). Así, ratas macho Wistar se dividieron en 2 grupos. El grupo control (C, n=9) se alimentó con pienso de laboratorio mientras que el grupo obeso, con dieta de cafetería (62% de lípidos por peso seco). El grupo alimentado con la dieta de cafetería se subdividió en 2 nuevos subgrupos (obeso, O; y obeso+trecadrine, O+T, cada uno n=9) y se les administró diariamente suero fisiológico o trecadrine por vía i.p. (1 mg/kg/ día), respectivamente. Las subpoblaciones linfocitarias y el ensayo de proliferación linfocitaria se determinaron mediante técnicas convencionales. El tratamiento con tracadrine consiguió prevenir la acumulación de grasa en las ratas alimentadas con dieta de cafetería. Además, la administración del agonista adrenérgico β3 mejoró ligeramente la proporción de las subpoblaciones linfocitarias comparado con los animales que sólo recibieron la dieta de cafetería, siendo similares a los valores de las ratas control. Sin embargo, la respuesta linfoproliferativa después del estímulo de diferentes mitógenos, se redujo considerablemente por la ingestión de la dieta de cafetería y el tratamiento con trecadrine produjo una reducción aún más marcada. Los niveles de expresión del RNAm de UCP2, PPARγ y Ob-Rb se vieron afectados tanto por la dieta de cafetería como por el tratamiento con trecadrine. En resumen, la administración del agonista adrenérgico β3 da lugar a un aumento del número de linfocitos de bazo en ratas obesas, pero no consigue restaurar la actividad mitogénicas de los linfocitos.

Immunoneutralization and anti-idiotype production: two-sided applications of leptin

The neuroendocrine and immune systems are linked through a complex bi-directional network, in which hormones modify immune function, and the immune system, through the action of cytokines, affects neuroendocrine responses involved in the maintenance of body homeostasis. The adipocyte-derived, peptide hormone leptin is a pleiotropic molecule belonging to the helical cytokine family. On pp. 182-187, Matarese et al. suggest the possibility of new leptin-based therapeutic strategies for the treatment of both infection and autoimmune disease.