Study of AMPK regulation activity in amygdala from control animals and possible effects on food intake and energy expenditure

• Grant number: 14/16724-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2014
• End date: July 31, 2017
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Patrícia de Oliveira Prada
• Grantee: Gisele de Castro
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that regulates cellular and whole body energy balance. Several studies have shown that hypothalamic AMPK participates in the control of food intake in response to nutrients and hormones such as insulin, leptin and ghrelin. The increase in AMPK activity in hypothalamus is associated with increased food intake and its inhibition leads to reduced food intake. Although most studies have focused on AMPK regulation in the hypothalamus, recent evidences suggests that others regions of the central nervous system may contribute in the control of food intake and energy metabolism. These regions include amygdala, which is part of the dopaminergic reward system. However, there are no studies demonstrating the expression and regulation of AMPK activity in this region. Therefore, the first and second objectives of this study are to investigate the expression of AMPK in the CeA of the amygdala region by immunoblotting and immunohistochemistry; and investigate the phosphorylation and activity of AMPK in vivo in the amygdala, in response to nutrients such as glucose, 2-DG induced hipoglicopenia and refeeding after prolonged fasting in control animals. The third objective is to investigate whether there are changes in Thr172 phosphorylation and AMPK activity in vivo in response to hormones such as insulin and ghrelin in the amygdala of control animals. The fourth objective is to investigate whether pharmacological inhibtion of AMPK (STO-609 and CaMKK inhibitor compound C) and activation (AICAR) for 7 days alter food intake, body weight, adiposity and energy expenditure from control animals by modulating the phosphorylation at Thr172 and enzyme activity in vivo. In addition and to increase the specificity of inhibition or activation, the fifth objective is to investigate whether chronic inhibition of AMPK expression with siRNA or by the injection of constitutively active AMPK (adenovirus) in the amygdala alters food intake, body weight, adiposity , energy expenditure and expression of neuropeptides from control animals. The sixth objective of the project is to investigate whether the melanocortin system regulates food intake and body weight by modulating AMPK. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CASTRO, Gisele de. Regulation of AMP-activated protein kinase (AMPK) in the CeA and the effects on food intake control and energy expenditure. 2017. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.