Figure 5.

AMPK-regulated control of feeding behavior by modulation of neuropeptide Y-and agouti-related protein-expressing neurons (NPY/AgRP neurons) and pro-opiomelanocortin neurons (POMC neurons), as proposed by Yang et al¹⁰³. A) in the fasted state ghrelin, a “hunger signal” derived from the stomach, activates AMPK in the presynaptic neurons acting upstream of NPY/AgRP neurons via the CaMKKβ pathway. This causes release of Ca²⁺ by Ca²⁺-induced release from intercellular stores via ryanodine receptors, creating a feedback loop that causes continued release of neurotransmitter onto the NPY/AgRP neuron, even when ghrelin stimulation ceases. The NPY/AgRP neurons promote feeding (and inhibits the POMC neurons, which inhibit feeding). b) Feeding continues (even in the absence of ghrelin) until the POMC neurons are stimulated by the “satiety signal”, leptin. Activity of these neurons inhibits feeding and also promotes release of opioids that inhibit AMPK in the presynaptic neurons upstream of the NPY/AgRP neurons, switching them back to an inactive state.