Document Detail

The hyperphagic effect of ghrelin is inhibited in mice by a diet high in fat.
MedLine Citation:
PMID:  20178795     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Ghrelin is the only peripheral hormone known to increase food intake. It is released from the stomach and is thought to function as a signal of energy deficit and a meal initiator. We generated transgenic mice in which levels of bioactive ghrelin are increased in the stomach and circulation. These mice, as expected, are hyperphagic and glucose intolerant. We investigated whether exposure to a high-fat diet (HFD) would exacerbate this phenotype. METHODS: We investigated the effect of HFD on energy and glucose homeostasis in ghrelin transgenic mice. We determined dietary preference; expression of hypothalamic neuropeptides that control food intake; and, using fast-performance liquid chromatography, the circulating forms of ghrelin. We measured food intake during continuous administration of ghrelin in wild-type mice fed either regular chow or an HFD. RESULTS: Ghrelin transgenic mice were resistant to diet-induced obesity because of their reduced food intake. This was not caused by alterations to food preference, hypothalamic signaling of neuropeptides that control food intake, or the form of circulating acylated ghrelin. Long-term administration of ghrelin to wild-type mice failed to increase ingestion of an HFD but, as expected, increased intake of regular chow. CONCLUSIONS: This is the first report that diets high in fat inhibit the hyperphagic effect of ghrelin; these findings indicate that features of the diet are important determinants of ghrelin's function. This information is important for the development of anti-obesity drugs that target ghrelin signaling.
James V Gardiner; Daniel Campbell; Michael Patterson; Aysha Kent; Mohammed A Ghatei; Stephen R Bloom; Gavin A Bewick
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-20
Journal Detail:
Title:  Gastroenterology     Volume:  138     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2468-76, 2476.e1     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
Department of Investigative Medicine, Hammersmith Campus, Imperial College London, London, UK.
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MeSH Terms
Dietary Fats / administration & dosage*
Energy Intake
Energy Metabolism
Ghrelin / pharmacology*
Hyperphagia / chemically induced,  prevention & control*
Insulin Resistance
Mice, Inbred C57BL
Mice, Inbred CBA
Motor Activity
Grant Support
072643/Z/03/Z//Wellcome Trust; G7811974//Medical Research Council
Reg. No./Substance:
0/Dietary Fats; 0/Ghrelin

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