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.
  
  
  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.
authors.affiliation: Department of Investigative Medicine, Hammersmith Campus, Imperial College London, London, UK.
authors.forename: Gavin A
authors.initials: GA
authors.lastname: Bewick
authors.forename: Aysha
authors.initials: A
authors.lastname: Kent
authors.forename: Daniel
authors.initials: D
authors.lastname: Campbell
authors.forename: Michael
authors.initials: M
authors.lastname: Patterson
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Ghatei
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: James V
authors.initials: JV
authors.lastname: Gardiner
mesh_terms: D000818:Animals; D001066:Appetite / Q000235:genetics / Q000502:physiology; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000235:genetics*; D006963:Hyperphagia / Q000235:genetics* / Q000378:metabolism; D020738:Leptin / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D020738:Leptin