[HTML][HTML] Absence of ghrelin protects against early-onset obesity

KE Wortley, JP del Rincon, JD Murray… - The Journal of …, 2005 - Am Soc Clin Investig
KE Wortley, JP del Rincon, JD Murray, K Garcia, K Iida, MO Thorner, MW Sleeman
The Journal of clinical investigation, 2005Am Soc Clin Investig
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 …
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.
The Journal of Clinical Investigation