Enterostatin in the Gastrointestinal Tract - Production and Possible Mechanism of Action

Abstract: The presence of procolipase and enterostatin in the rat gastrointestinal tract has been investigated. Procolipase was identified, using in situ hybridization and immunohistochemistry, in exocrine cells of the pancreas as well as in chief cells of the fundus region of the stomach. Enterostatin is the activation peptide of procolipase and it has been found to act as a satiety signal for fat. Using antibodies directed towards the C-terminal part of enterostatin, the peptide was found to be present in endocrine cells in the antral part of the stomach and in the upper small intestine. Double immunostaining showed enterostatin and serotonin to co-localize in a subpopulation of enterochromaffine cells. Cloning of rat gastric procolipase from a rat stomach cDNA library, revealed a sequence identical to pancreatic procolipase. Gastric procolipase was found to be secreted into the gastric juice and cleaved into enterostatin and colipase. Pepsin and acid were found to be involved in the cleavage. The expression of gastric procolipase during high-fat feeding was reduced in contrast to pancreatic procolipase. Secretion of procolipase to the gastric juice was, however unaffected by high-fat feeding. The role of gastric procolipase may be to prepare lipase-catalyzed fat digestion in the intestine. Gastric enterostatin may be involved in the onset of early satiety. After purification of enterostatin from the rat gut and pancreas by various chromatographic steps including HPLC analysis, two forms of enterostatin were identified with the amino acid sequences APGPR and VPGPR, in agreement with data from the cloning of rat pancreatic procolipase. APGPR was the most abundant form of enterostatin, whereas only small amounts of VPGPR were identified. Chronic intraperitoneal treatment of rats with enterostatin (APGPR) for one week resulted in decreased fat intake and decreased body weight gain. Enterostatin displayed its biological effect in reducing fat intake when the dietary fat corresponded to 38% of the total energy intake. In situations where dietary fat was provided in lower amounts, enterostatin was ineffective. The physiological significance of enterostatin was illustrated by the observation that within a group of rats fed a high-fat diet, the amount of pancreatic colipase was inversely related to the fat intake. In the pursuit of a receptor for enterostatin, binding studies to brain membranes indicated a two-site binding model with one high-affinity and one low-affinity binding site. In conclusion, the data presented in this study support the hypothesis that enterostatin plays an important role as a physiological satiety signal produced in the gastrointestinal tract.