Enterostatin--a peptide regulating fat intake.
A high fat intake, together with an inability to match lipid oxidation to fat intake, has been found to be correlated with obesity in humans. This review describes our current understanding of enterostatin, a peptide that selectively reduces fat intake. Enterostatin is formed in the intestine by the cleavage of secreted pancreatic procolipase, the remaining colipase serving as an obligatory cofactor for pancreatic lipase during fat digestion. Enterostatin is also produced in the gastric mucosa and the mucosal epithelia of the small intestine. Procolipase gene transcription and enterostatin release into the gastrointestinal lumen are increased by high-fat diets. After feeding, enterostatin appears in the lymph and circulation. Enterostatin will selectively inhibit fat intake during normal feeding and in experimental paradigms that involve dietary choice. Its anorectic effect has been demonstrated in a number of species. Both peripheral and central sites of action have been proposed. The peripheral mechanism involves an afferent vagal signaling pathway to hypothalamic centers. The central responses are mediated through a pathway that includes both serotonergic and opioidergic components. Chronically, enterostatin reduces fat intake, bodyweight, and body fat. This response may involve multiple metabolic effects of enterostatin, which include a reduction of insulin secretion, an increase in sympathetic drive to brown adipose tissue, and the stimulation of adrenal corticosteroid secretion. A possible pathophysiological role is suggested by studies that have linked low enterostatin production and/or responsiveness to strains of rat that become obese and prefer dietary fat. Humans with obesity also exhibit a lower secretion of pancreatic procolipase after a test meal, compared with persons of normal weight.
Erlanson-Albertsson
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Department of Cell and Molecular Biology, University of Lund, Sweden.
York
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D000818:Animals; D003089:Colipases / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004792:Enzyme Precursors; D006706:Homeostasis; D006801:Humans; D009765:Obesity; D011498:Protein Precursors / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*
D003089:Colipases; D004792:Enzyme Precursors; D011498:Protein Precursors; C037107:procolipase