Absence of ghrelin protects against early-onset obesity.
The gut peptide ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, has been implicated not only in the regulation of pituitary growth hormone (GH) secretion but in a number of endocrine and nonendocrine functions, including appetitive behavior and carbohydrate substrate utilization. Nevertheless, recent genetic studies have failed to show any significant defects in GH levels, food intake, or body weight in adult ghrelin-deficient (Ghrl-/-) mice. Here we demonstrate that male Ghrl-/- mice are protected from the rapid weight gain induced by early exposure to a high-fat diet 3 weeks after weaning (6 weeks of age). This reduced weight gain was associated with decreased adiposity and increased energy expenditure and locomotor activity as the animals aged. Despite the absence of ghrelin, these Ghrl-/- mice showed a paradoxical preservation of the GH/IGF-1 axis, similar to that reported in lean compared with obese humans. These findings suggest an important role for endogenous ghrelin in the metabolic adaptation to nutrient availability.
Wortley
Katherine E
KE
Regeneron Pharmaceuticals Inc., Tarrytown, New York, USA.
del Rincon
Juan-Pablo
JP
Murray
Jane D
JD
Garcia
Karen
K
Iida
Keiji
K
Thorner
Michael O
MO
Sleeman
Mark W
MW
D000821:Animal Feed; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002151:Calorimetry; D002241:Carbohydrates / Q000737:chemistry; D004032:Diet; D005838:Genotype; D054439:Ghrelin; D013006:Growth Hormone / Q000378:metabolism; D006579:Heterozygote; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D009479:Neuropeptides / Q000737:chemistry; D009765:Obesity / Q000235:genetics*; D010100:Oxygen / Q000378:metabolism; D036361:Peptide Hormones / Q000378:metabolism / Q000502:physiology*; D010641:Phenotype; D010902:Pituitary Gland / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D002241:Carbohydrates; D054439:Ghrelin; D008024:Ligands; D009479:Neuropeptides; D036361:Peptide Hormones; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D010100:Oxygen