Regulation of food intake: The gastric X/A-like endocrine cell in the spotlight

Abstract

Nutritional status influences hormone secretion from specialized enteroendocrine cells within the gut mucosa. These hormones regulate food intake by mediating information to central neurocircuitries in the brainstem and forebrain (eg, hypothalamic nuclei). Intestinal enteroendocrine cells were believed to be the main source of gut peptides regulating food intake. However, recent evidence highlights a specific endocrine cell within the oxyntic glands of the stomach as an important player in appetite control. Acylated ghrelin is the only known orexigenic hormone peripherally produced in gastric X/A-like cells and centrally acting to stimulate food intake. Recent advances led to the assumption that des-acylated ghrelin, coreleased with acylated ghrelin, is also involved in regulating food intake. This, and the novel observation that nesfatin-1, which inhibits food intake, is expressed in ghrelin-producing cells of the stomach, supports an important role for gastric X/A-like cells in regulating food intake. Another peptide, obestatin, was initially described as a ghrelin gene product inhibiting food intake, but subsequent studies produced controversial data and its action as an anorexic factor is doubtful. Importantly, synergistic interactions between ghrelin and intestinal peptides seem to orchestrate food intake and body weight regulation, which may have implications for understanding mechanisms leading to the treatment of obesity.