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Current Medicinal Chemistry - Central Nervous System Agents

Editor-in-Chief

ISSN (Print): 1568-0150
ISSN (Online): 1875-6158

Fat Digestion and its Role in Appetite Regulation and Energy Balance -The Importance of Enterostatin and Tetrahydrolipstatin

Author(s): Andreas Lindqvist and Charlotte Erlanson-Albertsson

Volume 3, Issue 3, 2003

Page: [157 - 175] Pages: 19

DOI: 10.2174/1568015033477712

Price: $65

Abstract

A high fat intake, together with an inability to match lipid utilization of a high-fat intake, is correlated with obesity in man. In this review enterostatin, a peptide, which specifically reduces fat intake, is described. Enterostatin is formed in the intestine by the cleavage of pancreatic procolipase, the remaining colipase serving as an obligatory cofactor for pancreatic lipase during fat digestion. Enterostatin is also produced in chief cells of the stomach as part of procolipase as well as in enterochromaffine cells independent of procolipase, most frequent in the antral part of the stomach extending all along the intestine down to the ileum. Enterostatin has been found to increase during fat feeding, where it is found in the intestinal lumen, in the lymph as well as in the circulating blood. When reducing food intake, enterostatin behaves as a physiological satiety substance, inducing early satiety. A raised production of serotonin has been measured centrally. During long-term treatment, enterostatin has been found to reduce body weight in the rat and mouse. A reduced body weight may be explained by a decreased food intake and an increased energy expenditure through activation of the sympathetic nervous system and increased expression of uncoupling protein 1 in brown adipose tissue. Enterostatin also increases the expression of uncoupling protein 2 in the gastrointestinal tract. The mechanism of action of enterostatin suggests the involvement of the opioid system being inhibited by enterostatin. Another target protein for enterostatin is the beta-subunit of F1F0-ATPase. These two target proteins may explain the appetite regulating effects of enterostatin as well as the thermogenic effects.

Keywords: fat intake, insulin, body weight, obesity, pancreas, colipase


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