Obesity and depression in the post-menopause: study in rats about the effects of ovariectomy on behavioral aspects and parameters of the central regulation of feeding

Abstract

Obesity and depression represent complex chronic disorders whose real causes are not completely understood. They both are at present important public health issues leading to relevant impairment of quality of life. It is known that the obesity epidemic brings a myriad of complications such as type 2 diabetes, cardiovascular diseases, etc. Depression prevalence has also increased in the past years and the Global Health Organization has recently estimated that, by the year 2030, depression will be the most prevalent disease worldwide. The developing countries are likely to be the most affected, suffering a high economical burden due to the high costs of disease treatment allied to the losses brought by the decreased productivity of the affected individuals. Recent data indicate that this fact may already be happening in Brazil, with São Paulo state showing a high depression rate. Efforts towards the understanding of the disturbances involved in these two pathologies are, thus, very valuable. Importantly, there is strong evidence that obesity and depression are connected in the population. The post menopausal period is a time in women's life with increased prevalence of both conditions, perhaps due to their association. However, very little is known about the molecular mechanisms responsible for these relations and their elucidation would be extremely important and could lead to the identification of potential targets for preventive as well as therapeutic interventions.Many of the central mediators controlling the homeostatic and hedonic components of feeding regulation act at the hypothalamus and hippocampus and also affect emotional processes, with serotonergic and peptidergic systems being relevant mediators. Finally, inflammatory mediators seem to be importantly involved in both obesity and depression. The above considerations attest the relevance of evaluating the molecular mechanisms involved in obesity and depression and in their association. The present study has the objective of further elucidating the important interfaces between the CNS control of feeding and emotional aspects, also exploring the influence of nutritional factors on this relations. This subject is currently highly relevant and the proposed approach is at the frontier of the research about these pathologies, which need to be better understood on their molecular aspects. The present project is thus aimed at studying molecular aspects involved in the obesity/depression interaction that develops after menopause, focusing on the participation of the central serotonergic and peptidergic systems of the CNS control of feeding as well on the influence of inflammatory status and dietary factors on these relations.Using the ovariectomy model in rats, we will evaluate:- during 8 weeks since ovariectomy or sham-ovariectomy, body weight and intake of control diet or of diets enriched with either lard or fish-oil.At the end of the 8 weeks we will evaluate: - behavioral tests for signs of depression/anxiety- body fat- plasma hormones and metabolic parameters- food intake after intracerebroventricular serotonin injection- hypothalamic and hippocampal amount of serotonin and 5-hydroxiindolacetic acid- hypothalamic and hippocampal gene and protein expression of:a) feeding control mediators: SR-1B e SR-2C receptors, ST, NPY, AgRP, POMC, CART and leptin and adiponectin receptorsb) inflammatory mediators: IL-6, IL-10, TNF-alfa, TLR2 e TLR4. (AU)