Study of AMPK regulation activity in amygdala from control animals and possible ef...
| Grant number: | 15/00343-0 |
| Support type: | Regular Research Grants |
| Duration: | June 01, 2015 - November 30, 2017 |
| Field of knowledge: | Health Sciences - Medicine |
| Principal Investigator: | Patrícia de Oliveira Prada |
| Grantee: | Patrícia de Oliveira Prada |
| Home Institution: | Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil |
Abstract
Obesity is now one of the most important public health problems in the world, the most important risk factor for the development of various comorbidities. Body weight is maintained through a balance between food intake and energy expenditure. The increased activity of AMP-activated protein kinase (AMPK) in hypothalamic nuclei is associated with increased food intake. In recent years, other areas of the central nervous system such as dopaminergic reward system have been investigated for contributing to the regulation of energy metabolism. Among these areas, the amygdala is known for being responsive to nutrients and hormones such as insulin and ghrelin. However, there are no studies demonstrating the expression and activity of AMPK regulation in this region, as well as the participation of amygdala AMPK in the control of energy metabolism. In this sense, in control animals, we propose (1) to investigate the expression and regulation of phosphorylation of Thr172 and AMPK activity in the amygdala in vivo in response to nutrients (glucose), neuroglycopenia (induced by 2-DG), reefeding after prolonged fasting and in response to hormones (insulin and ghrelin). (2) To investigate whether AMPK participates in the control of energy metabolism resulting from the activation or inactivation of the melanocortin system in the amygdala in vivo. In other purpose, (3) to investigate whether the pharmacological blockade (STO-609-inhibitor CaMKK and Compound C) or activation (ARA) of AMPK for 7 days alter food intake, body weight, adiposity, energy expenditure and expression of neuropeptides. In addition and to increase the specificity, (4) to investigate whether chronic inhibition of expression with siRNA or active constitutive expression of AMPK adenovirus in the amygdala changes the food intake, body weight, adiposity, energy expenditure and neuropeptide expression. Following the characterization of control animals, (5) to investigate the expression and regulation of AMPK in CeA region of animals receiving high fat diet chronically and Zucker rats with genetic obesity. If AMPK is more active in the amygdala of these animals, (6) to investigate whether the inhibition of AMPK expression in this region can change parameters such as body weight, fat mass, food intake, energy expenditure, glucose tolerance, insulin sensitivity, measured by euglycemic hyperinsulinemic clamp and hepatic glucose production. (AU)