The Role of Enterostatin in Eating Behavior and Diet

Abstract

Enterostatin is the amino terminal pentapeptide produced by proteolytic cleavage of pancreatic procolipase and released into the small intestine during digestion of fat catalyzed by pancreatic lipase and its protein cofactor colipase. Enterostatin specifically suppresses fat intake or high-fat intake as opposed to high-carbohydrate diets. Procolipase and enterostatin have also been localized to the gastric mucosa, as well as to certain brain regions, such as amygdala, hypothalamus, and cortex. The mechanism for the decreased fat intake is dependent on cholecystokinin pathways as well as melanocortin pathways, which involves an inhibition of gastric motility in the intestine, a release of serotonin centrally and a suppression of the fat-specific hunger hormone, agouti-related peptide (AgRP). The expression of enterostatin is impaired by the presence of sucrose in the diet. Enterostatin also displays metabolic effects, such as inhibition of insulin secretion and lowering of serum cholesterol levels. Thermogenesis is likewise stimulated through an activation of sympathetic drive to brown adipose tissue with induced expression of uncoupling protein 1. The receptor for enterostatin is the β-subunit of F1-ATPase being localized to the plasma membrane in target cells. Following activation of the receptor with enterostatin various intracellular pathways are activated leading to a perturbed ATP/ADP ratio, an activation of cAMP, AMPkinase as well as MAPkinase. Enterostatin and fatty acids cause an increased expression of the receptor on the plasma membrane. No effect on food intake has been demonstrated in human beings when enterostatin is given in single doses. With green plants proteins, which induce an endogenous release of enterostatin, satiety is promoted in human beings. An enterostatin-deficient mouse has elevated plasma cholesterol levels, pointing to the role of enterostatin in reducing blood lipids. The fact that the production of enterostatin and its receptor is strongly stimulated by dietary fat suggests that enterostatin works as a feedback signal in promoting regulation of fat intake and utilization of fat as energy substrate.