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Abstract

Cell biology studies on gastric leptin secretion have demonstrated that the hormone known to regulate appetite and food intake, is synthesized, packaged in granules and discharged through regulated secretion into the gastric lumen by the Chief cells of the gastric mucosa. Leptin present in the gastric juice is tightly associated to the soluble isoform of its receptor. The leptin-leptin receptor complex allows the leptin molecule to survive the harsh conditions of the gastric juice. Leptin vehiculated from the gastric cavity to the duodenal lumen interacts with membrane-bound leptin receptors located on the apical membrane of the duodenal epithelial cells. Leptin is then internalized and released at the basal pole of the intestinal cells towards the submucosa. It penetrates the blood stream and reaches its hypothalamic target cells where regulation of food intake takes place. Since leptin is normally present in the gastric juice, we evaluated the efficiency of an oral administration of exogenous leptin for the control of food intake. Experiments were performed on normal and obese rodents as well as on large mammals, pigs and dogs. Exogenous leptin given orally in the form of a pill is able to reduce food intake and to trigger weight loss in all animals. Compared to leptin secreted by the adipose tissue, gastric leptin appears as an important and favorabletargetfor clinical application.

Biography

Email: moise.bendayan@umontreal.ca