Numerous
peptides released from endocrine cells in the intestinal mucosa were established early on to be involved in the physiological regulation of food intake with a prominent role in termination of food ingestion when nutrients pass along the intestinal tract. Recently,
peptides released from X/A-like endocrine cells of the gastric oxyntic mucosa were recognized as additional key players in the regulation of feeding and energy expenditure. Gastric X/A-like cells release the octanoylated
peptide,
ghrelin, the only known peripherally produced
hormone stimulating food intake through interaction with
growth hormone secretagogue 1a receptor (GHS-R1a). Additionally, non-octanoylated (
des-acyl) ghrelin present in the circulation at higher levels than
ghrelin is currently discussed as potential modulator of food intake by opposing
ghrelin's action independent from
GHS-R1a although the functional significance remains to be established.
Obestatin, a
ghrelin-associated
peptide was initially reported as anorexigenic modulator of
ghrelin's orexigenic action. However, subsequent reports did not support this contention. Interesting is the recent identification of nesfatin-1, a
peptide derived from the nucleobindin2 gene prominently expressed in gastric X/A-like cells in different vesicles than
ghrelin. Circulating nesfatin-1 levels vary with metabolic state and peripheral or central injection inhibits dark phase feeding in rodents. Overall, these data point to an important role of gastric X/A-like cells in food intake regulation through the expression of the orexigenic
peptide ghrelin along with
des-acyl ghrelin and nesfatin-1 capable of reducing food intake upon exogenous injection although their mechanisms of action and functional significance remain to be established.