MODULATION OF THE S6KS EXPRESSION IN THE CENTRAL NERVOUS SYSTEM FOR STUDIES RELATED TO CONTROL OF FOOD INTAKE AND ENERGY EXPENDITURE

TAVARES, MARIANA ROSOLEN; LEMES, SIMONE FERREIRA; RODRIGUES, HOSANA GOMES; PRADA, PATRICIA OLIVEIRA; SIMABUCO, FERNANDO MOREIRA

Foz do Iguaçu, Paraná

Congreso; 4th Annual Meeting of the Brazilian Society for Biochemistry and Molecular Biology (SBBq); 2015

INTRODUCTION Obesity has been considered a worldwide epidemic. World Health Organization (WHO) data are categorical to assert that obesity is related to a number of diseases, including: diabetes mellitus type II, cardiovascular disease, cerebrovascular accident (CVA), dyslipidemia and some types of cancer. Thus, there is currently great demand for a better understanding of the biochemical and metabolic processes related to obesity. The signaling pathway of mTOR protein has been associated with the control of energy balance in the body, working as a sensor of the amount of nutrients available and signaling to the expenditure of the stored energy. OBJECTIVES The present study aims to investigate the roles of S6Ks, known effectors of mTOR, in the central nervous system (CNS) and the consequences for energy homeostasis. MATERIALS AND METHODS We produced adenovirus type 5 vectors deficient in replication, carrying the genes of S6Ks, aiming to overexpress these proteins in vitro and in vivo. DISCUSSION AND RESULTS The results in vitro indicate that the stimulation with insulin activates mTOR/S6Ks signaling pathway, and this effect is inhibited by treatment of the cells with rapamycin, a known mTOR inhibitor. Importantly, overexpression of S6Ks isoforms (p70-S6K1, p85-S6K1 and p54-S6K2) increased the basal phosphorylation of S6, one of S6Ks targets. Besides, these adenoviral vectors were able to transduce hypothalamic cells GT1-7 in vitro. These data demonstrate the effectiveness of adenoviral vectors to drive the overexpression of different isoforms S6Ks. Preliminary data of the injection of adenoviral vectors in the hypothalamus of Swiss animals suggest expression of the S6Ks and GFP reporter protein. CONCLUSIONS Experiments will be conducted to verify possible different functions of S6Ks related to the central control of energy homeostasis. Supported by : FAPESP. Keywords: mTOR, S6Ks, metabolism