Regulation of AMP-activated protein kinase (AMPK) in the CeA and the effects on food intake control and energy expenditure

Author(s)

Gisele de Castro

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas
• Defense date: 2017-11-30

Examining board members

Patrícia de Oliveira Prada; Marcio Alberto Torsoni; Marcelo Alves Mori; Lucila Leico Kagohara Elias; Ivan Eid Tavares de Araújo

• Advisor: Patrícia de Oliveira Prada

Abstract

AMP-activated protein kinase (AMPK) is a cellular energy sensor that regulates energy balance at cellular and whole body nivel. Several studies demonstrate that hypothalamic AMPK participates in the control of food intake in response to nutrients and hormones such as insulin and ghrelin. Increased AMPK activity in hypothalamus is associated with enhance in food intake and its inhibition leads to reduced food intake. Recent evidence demonstrates that other regions from central nervous system may contribute to control energy metabolism and food intake. The central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and jointly with the hypothalamus participates in control of food intake. In amygdala molecular pathways such as insulin pathway participate in the control of food intake, however other cellular pathways, such as AMPK may contribute to this control. In this sense, the present study investigated AMPK activation in CeA and its participation in food intake control. Fasting increased phosphorylation in Thr172 of AMPK?1/2 and refeeding reduced this phosphorylation. Injection of glucose in CeA decreased the phosphorylation in Thr172 of AMPK?1/2, whereas 2DG injection increased this phosphorylation as well as food intake. Ghrelin injection in CeA increased food intake and Thr172 phosphorylation of AMPK?1/2. In adiction, NPY gene expression was increased and oxytocin gene expression was lower. In contrast, insulin reduced Thr172 phosphorylation of AMPK?1/2 in CeA. As expected, AMPK pharmacological activation in CeA with AICAR increased food intake. Chronic injection of MTII in CeA reduced body mass, food intake and phosphorylation in Thr172 of AMPK?1/2. Further, knocking down Alpha 1/2 AMPK in the CeA for 14 days was sufficient to decrease body mass without altering food intake. AMPK?2 and NPY gene expression in CeA was reduced and oxytocin gene expression in CeA and UCP-1 in BAT was increased. These results suggest that once active in CeA, AMPK participates in control of energy homeostasis by modulating food intake in response to nutrients and hormones such as ghrelin and insulin (AU)

• FAPESP's process: 14/16724-0 - Study of AMPK regulation activity in amygdala from control animals and possible effects on food intake and energy expenditure
• Grantee: Gisele de Castro
• Support Opportunities: Scholarships in Brazil - Doctorate