Efecto del estrés durante diferentes etapas del ciclo vital sobre el desarrollo de obesidad inducida por la dieta

Resumen

THE EFFECT OF STRESS DURING DIFFERENT LIFE STAGES ON THE DEVELOPMENT OF DIET-INDUCED OBESITY. Laura Paternain Markinez. School of Pharmacy. University of Navarra (Spain). 2011. The stress has been reported as a widespread problem and several studies have linked it with obesity, diabetes and inflammation-related diseases. Thus, situations of chronic stress in different stages during the life cycle, such as prenatal, early-life or adult periods, have been involved in metabolic disorders in adulthood, which implies not only peripheral tissues but also hypothalamic appetite and energy balance regulation systems. With this background, the aim of this study was to analyse in adult rats the possible effect of stressful experiences at different stages of life on the development of diet-induced obesity. For this purpose, 3 different experimental models were carried out: chronic-mild stress (CMS) during adulthood, maternal separation (MS) during lactation and a prenatal stress (PNS) during the third week of gestation. All these models were accompanied with a dietary treatment with a hypercaloric diet in adulthood. Consuming a hypercaloric diet induced phenotypical changes as increased body weight, adiposity and different biochemical parameters as serum leptin levels and insulin resistance markers. The stress paradigms induced different responses to a hypercaloric diet in adult rats, reducing adiposity in maternal separation and chronic-mild stress and increasing it in prenatal stress. MS reduced insulin resistance markers only in chow fed rats and prenatal stress increased them. The lipid profile was also reduced by different stress protocols and the same result was obtained in serum corticosterone levels. However, faecal corticosterone was increased due to the stress protocols. The nutrigenomic study performed in adipose tissue identified alterations in lipolysis, lipogenesis and inflammation pathways due to the intake of hypercaloric diets and the stress protocols. Moreover, a tissue and depot-specific pattern was observed in different genes related to glucocorticoid metabolism because of the treatments. Only in PNS animals has a higher energy intake due to the stress paradigm, thus involved modifications in the reward system (Dopamine active transporter, Slc6a3), insulin resistance (Insulin receptor) and food intake related genes (Neuropeptide Y and Proopiomelanocortin, POMC) in the hypothalamus. In relation to Slc6a3 and POMC, changes in the methylation levels of these promoter regions were observed. This study has shown that adverse situations during different life stages in rats can induce different metabolic adaptations. These metabolic changes, in turn, can influence the response to a hypercaloric diet during adulthood and may induce obesity and/or different comorbidities associated with obesity.