Multiple metabolic signals in the CeA regulate feeding: The role of AMPK

Gisele Castro; Natália Ferreira Mendes; Laís Weissmann; Paula Gabriele Fernandes Quaresma; Mario Jose Abdalla Saad; Patricia Oliveira Prada

doi:10.1016/j.mce.2024.112232

Multiple metabolic signals in the CeA regulate feeding: The role of AMPK

Mol Cell Endocrinol. 2024 Apr 10:589:112232. doi: 10.1016/j.mce.2024.112232. Online ahead of print.

Authors

Gisele Castro¹, Natália Ferreira Mendes², Laís Weissmann¹, Paula Gabriele Fernandes Quaresma¹, Mario Jose Abdalla Saad¹, Patricia Oliveira Prada³

Affiliations

¹ Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
² Department of Translational Medicine (Section of Pharmacology), School of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.
³ Department of Internal Medicine, School of Medical Science, State University of Campinas (UNICAMP), Campinas, SP, Brazil; School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, SP, Brazil; Biology Institute, State University of Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address: pprada@unicamp.br.

PMID: 38604549
DOI: 10.1016/j.mce.2024.112232

Abstract

Background: The central nucleus of the amygdala (CeA) is part of the dopaminergic reward system and controls energy balance. Recently, a cluster of neurons was identified as responsive to the orexigenic effect of ghrelin and fasting. However, the signaling pathway by which ghrelin and fasting induce feeding is unknown. AMP-activated protein kinase (AMPK) is a cellular energy sensor, and its Thr172 phosphorylation (AMPKThr172) in the mediobasal hypothalamus regulates food intake. However, whether the expression and activation of AMPK in CeA could be one of the intracellular signaling activated in response to ghrelin and fasting eliciting food intake is unknown.

Aim: To evaluate the activation of AMPK into CeA in response to ghrelin, fasting, and 2-deoxy-D-glucose (2DG) and whether feeding accompanied these changes. In addition, to investigate whether the inhibition of AMPK into CeA could decrease food intake.

Methods: On a chow diet, eight-week-old Wistar male rats were stereotaxically implanted with a cannula in the CeA to inject several modulators of AMPKα1/2Thr172 phosphorylation, and we performed physiological and molecular assays.

Key findings: Fasting increased, and refeeding reduced AMPKThr172 in the CeA. Intra-CeA glucose injection decreased feeding, whereas injection of 2DG, a glucoprivation inductor, in the CeA, increased food intake and blood glucose, despite faint increases in AMPKThr172. Intra-CeA ghrelin injection increased food intake and AMPKThr172. To further confirm the role of AMPK in the CeA, chronic injection of Melanotan II (MTII) in CeA reduced body mass and food intake over seven days together with a slight decrease in AMPKThr172.

Significance: Our findings identified that AMPK might be part of the signaling machinery in the CeA, which responds to nutrients and hormones contributing to feeding control. The results can contribute to understanding the pathophysiological mechanisms of altered feeding behavior/consumption, such as binge eating of caloric-dense, palatable food.

Keywords: 2DG; AMPK; Central nucleus of the amygdala (CeA); Fasting; Food intake; Ghrelin.