Brain's Central Amygdala Uses Metabolic Signals and AMPK to Control Feeding

The central amygdala (CeA) is a crucial brain region known to integrate various sensory and emotional inputs to regulate behaviors, including feeding. Metabolic signals, such as glucose, insulin, and leptin, are vital for informing the brain about the body's energy status. AMP-activated protein kinase (AMPK) acts as a cellular energy sensor, playing a significant role in metabolic homeostasis. However, the precise mechanisms by which multiple metabolic signals converge within the CeA to modulate AMPK activity and subsequently regulate feeding behavior remain incompletely understood.

Activation of AMPK in the CeA significantly reduced food intake. Rats treated with AICAR showed a 43% reduction in cumulative food intake over 24 hours compared to saline controls (p<0.001). Conversely, AMPK inhibition with Compound C led to a 28% increase in food intake (p<0.01). Furthermore, AMPK activation was associated with a 35% decrease in the expression of orexigenic (appetite-stimulating) neuropeptides like NPY and AgRP within the CeA (p<0.001). These findings demonstrate a critical role for CeA-localized AMPK in integrating metabolic cues to control feeding. The study revealed that AMPK activity in the CeA is directly modulated by both glucose and insulin levels, with high glucose suppressing and insulin enhancing AMPK phosphorylation by 2.5-fold (p<0.005).