Hunger, ghrelin and the gut.

Hunger is defined as a craving or urgent need for food. Abundant evidence now indicates that homeostatic and cognitive mechanisms promote the sensation of hunger. Communication between the gastrointestinal (GI) tract and the central nervous system (CNS) regulate both homeostatic and cognitive mechanisms to control feeding behavior. In this context the GI derived feeding peptide ghrelin, targets the CNS to promote food anticipation, learning, hedonic feeding and motivation for food. Importantly meal expectation following nutrient deprivation or satiation is associated with elevation of plasma ghrelin, highlighting the propensity of each mechanism to stimulate GI ghrelin secretion. It is well established that multiple physiological processes control ghrelin secretion from the GI tract. For example activation of descending sympathetic and parasympathetic pathways, GI feeding peptides, metabolic factors and endocannabinoid signaling mechanisms all regulate ghrelin secretion. In parallel, activation of the CNS ghrelin receptor (GHSR-1a) controls food anticipation, food-based learning, spatial learning and the rewarding properties of food. Notably GHSR-1a is expressed within a network of CNS regions that regulate diverse aspects of feeding behavior. These examples suggest a redundancy regarding mechanisms that control GI ghrelin secretion and complexity for GHSR-1a-mediated regulation of food intake. Based on this collective data, we suggest that learned information linked to the receipt of food is transmitted from the CNS to the GI tract to stimulate ghrelin release. We further postulate that GI ghrelin release and ghrelin-GHSR-1a interactions adapt over time, metabolic status and environment to direct feeding behavior.