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

Gavin Bewick; Aysha Kent; Daniel Campbell; Michael Patterson; Mohammed A. Ghatei; Stephen R. Bloom; James V. Gardiner

doi:10.2337/db08-1428

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

Gavin Bewick, Aysha Kent, Daniel Campbell, Michael Patterson, Mohammed A. Ghatei, Stephen R. Bloom^*, James V. Gardiner

^*Corresponding author for this work

Imperial College London

Research output: Contribution to journal › Article › peer-review

58 Citations (Scopus)

Abstract

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 beta-cell function.

Original language	English
Pages (from-to)	840-846
Number of pages	7
Journal	Diabetes
Volume	58
Issue number	4
DOIs	https://doi.org/10.2337/db08-1428
Publication status	Published - Apr 2009

Keywords

CENTRALLY ADMINISTERED GHRELIN
HORMONE SECRETAGOGUE RECEPTOR
BROWN ADIPOSE-TISSUE
ARCUATE NUCLEUS
ENDOGENOUS GHRELIN
PANCREATIC-ISLETS
GH SECRETAGOGUE
TRANSGENIC MICE
ENERGY-BALANCE
FOOD-INTAKE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/db08-1428

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title = "Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity",

abstract = "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 beta-cell function.",

keywords = "CENTRALLY ADMINISTERED GHRELIN, HORMONE SECRETAGOGUE RECEPTOR, BROWN ADIPOSE-TISSUE, ARCUATE NUCLEUS, ENDOGENOUS GHRELIN, PANCREATIC-ISLETS, GH SECRETAGOGUE, TRANSGENIC MICE, ENERGY-BALANCE, FOOD-INTAKE",

author = "Gavin Bewick and Aysha Kent and Daniel Campbell and Michael Patterson and Ghatei, {Mohammed A.} and Bloom, {Stephen R.} and Gardiner, {James V.}",

year = "2009",

month = apr,

doi = "10.2337/db08-1428",

language = "English",

volume = "58",

pages = "840--846",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "4",

}

TY - JOUR

T1 - Mice With Hyperghrelinemia Are Hyperphagic and Glucose Intolerant and Have Reduced Leptin Sensitivity

AU - Bewick, Gavin

AU - Kent, Aysha

AU - Campbell, Daniel

AU - Patterson, Michael

AU - Ghatei, Mohammed A.

AU - Bloom, Stephen R.

AU - Gardiner, James V.

PY - 2009/4

Y1 - 2009/4

N2 - 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 beta-cell function.

AB - 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 beta-cell function.

KW - CENTRALLY ADMINISTERED GHRELIN

KW - HORMONE SECRETAGOGUE RECEPTOR

KW - BROWN ADIPOSE-TISSUE

KW - ARCUATE NUCLEUS

KW - ENDOGENOUS GHRELIN

KW - PANCREATIC-ISLETS

KW - GH SECRETAGOGUE

KW - TRANSGENIC MICE

KW - ENERGY-BALANCE

KW - FOOD-INTAKE

U2 - 10.2337/db08-1428

DO - 10.2337/db08-1428

M3 - Article

SN - 0012-1797

VL - 58

SP - 840

EP - 846

JO - Diabetes

JF - Diabetes

IS - 4

ER -

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

Abstract

Keywords

UN SDGs

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