Multiple metabolic signals in the CeA regulate feeding: The role of AMPK.
This animal study investigated whether AMP-activated protein kinase (AMPK) in the central nucleus of the amygdala (CeA) serves as an intracellular signaling mediator linking metabolic cues—ghrelin, fasting, and glucoprivation—to food intake regulation. Male Wistar rats were surgically implanted with cannulas in the CeA and received intra-CeA injections of various modulators, including glucose, 2-deoxy-D-glucose (2DG), ghrelin, and Melanotan II (MTII). The study measured AMPK phosphorylation at Thr172 (AMPKThr172) alongside food intake and body weight. Key findings attributed to the study include: fasting increased and refeeding reduced CeA AMPKThr172; intra-CeA glucose reduced food intake while 2DG (a glucoprivation inducer) increased food intake and blood glucose with modest AMPKThr172 elevation; intra-CeA ghrelin increased both food intake and AMPKThr172; and chronic intra-CeA MTII injection reduced body mass and food intake over seven days alongside a slight reduction in AMPKThr172. Limitations include use of a single rodent model, small and unspecified sample sizes per group, and the inability to establish direct causality between AMPK activation and feeding behavior. No human data were collected.
Why this grade: All experiments were conducted exclusively in male Wistar rats using stereotaxic cannula implantation; no human or clinical data were included.
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.
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