Ghrelin

acts as an endogenous antagonist at the MC4R to block the satiety effects of

-MSH during fasting; its lack of a role in the fed state is due to the

competitive binding of PYY 3-36 to the same receptor.

Ghrelin

utilizes fenestrated capillaries to act exclusively on the ventromedial

hypothalamus (VMH) to inhibit the "satiety center" during periods of

negative energy balance; it lacks a role in the fed state because tanycytes

form a physical barrier that prevents its entry into the hypothalamus when

plasma glucose is elevated.

Ghrelin

binds to the GHSR (Growth hormone secretagogue receptor) on POMC neurons to

stimulate the release of -endorphin as a fasting signal; it has no functional

role in the fed state because its secretion is inhibited.

Ghrelin

coordinates the hypothalamic response to fasting by activating the GHSR on

AgRP/NPY neurons to drive hunger and GABAergic inhibition of POMC activity;

this orexigenic circuit lacks a functional role in the fed state because

ghrelin levels are rapidly suppressed by nutrient ingestion.