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Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity

OBJECTIVE: Ghrelin is the only known peripheral hormone to increase ingestive behavior. However, its role in the physiological regulation of energy homeostasis is unclear because deletion of ghrelin or its receptor does not alter food intake or body weight in mice fed a normal chow diet. We hypothes...

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Autores principales: Bewick, Gavin A., Kent, Aysha, Campbell, Daniel, Patterson, Michael, Ghatei, Mohammed A., Bloom, Stephen R., Gardiner, James V.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661599/
https://www.ncbi.nlm.nih.gov/pubmed/19151202
http://dx.doi.org/10.2337/db08-1428
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author Bewick, Gavin A.
Kent, Aysha
Campbell, Daniel
Patterson, Michael
Ghatei, Mohammed A.
Bloom, Stephen R.
Gardiner, James V.
author_facet Bewick, Gavin A.
Kent, Aysha
Campbell, Daniel
Patterson, Michael
Ghatei, Mohammed A.
Bloom, Stephen R.
Gardiner, James V.
author_sort Bewick, Gavin A.
collection PubMed
description OBJECTIVE: Ghrelin is the only known peripheral hormone to increase ingestive behavior. However, its role in the physiological regulation of energy homeostasis is unclear because deletion of ghrelin or its receptor does not alter food intake or body weight in mice fed a normal chow diet. We hypothesized that overexpression of ghrelin in its physiological tissues would increase food intake and body weight. RESEARCH DESIGN AND METHODS: We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in the stomach and brain. We investigated the effect of ghrelin overexpression on food intake and body weight. We also measured energy expenditure and determined glucose tolerance, glucose stimulated insulin release, and peripheral insulin sensitivity. RESULTS: Ghrelin transgenic (Tg) mice exhibited increased circulating bioactive ghrelin, which was associated with hyperphagia, increased energy expenditure, glucose intolerance, decreased glucose stimulated insulin secretion, and reduced leptin sensitivity. CONCLUSIONS: This is the first report of a Tg approach suggesting that ghrelin regulates appetite under normal feeding conditions and provides evidence that ghrelin plays a fundamental role in regulating β-cell function.
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spelling pubmed-26615992010-04-01 Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity Bewick, Gavin A. Kent, Aysha Campbell, Daniel Patterson, Michael Ghatei, Mohammed A. Bloom, Stephen R. Gardiner, James V. Diabetes Original Article OBJECTIVE: Ghrelin is the only known peripheral hormone to increase ingestive behavior. However, its role in the physiological regulation of energy homeostasis is unclear because deletion of ghrelin or its receptor does not alter food intake or body weight in mice fed a normal chow diet. We hypothesized that overexpression of ghrelin in its physiological tissues would increase food intake and body weight. RESEARCH DESIGN AND METHODS: We used bacterial artificial chromosome transgenesis to generate a mouse model with increased ghrelin expression and production in the stomach and brain. We investigated the effect of ghrelin overexpression on food intake and body weight. We also measured energy expenditure and determined glucose tolerance, glucose stimulated insulin release, and peripheral insulin sensitivity. RESULTS: Ghrelin transgenic (Tg) mice exhibited increased circulating bioactive ghrelin, which was associated with hyperphagia, increased energy expenditure, glucose intolerance, decreased glucose stimulated insulin secretion, and reduced leptin sensitivity. CONCLUSIONS: This is the first report of a Tg approach suggesting that ghrelin regulates appetite under normal feeding conditions and provides evidence that ghrelin plays a fundamental role in regulating β-cell function. American Diabetes Association 2009-04 2009-01-16 /pmc/articles/PMC2661599/ /pubmed/19151202 http://dx.doi.org/10.2337/db08-1428 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Bewick, Gavin A.
Kent, Aysha
Campbell, Daniel
Patterson, Michael
Ghatei, Mohammed A.
Bloom, Stephen R.
Gardiner, James V.
Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity
title Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity
title_full Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity
title_fullStr Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity
title_full_unstemmed Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity
title_short Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity
title_sort mice with hyperghrelinemia are hyperphagic and glucose intolerant and have reduced leptin sensitivity
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2661599/
https://www.ncbi.nlm.nih.gov/pubmed/19151202
http://dx.doi.org/10.2337/db08-1428
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