Absence of ghrelin protects against early-onset obesity
Katherine E. Wortley, Juan-Pablo del Rincon, Jane D. Murray, Karen Garcia, Keiji Iida, Michael O. Thorner, Mark W. Sleeman
Katherine E. Wortley, Juan-Pablo del Rincon, Jane D. Murray, Karen Garcia, Keiji Iida, Michael O. Thorner, Mark W. Sleeman
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Research Article Metabolism

Absence of ghrelin protects against early-onset obesity

Abstract

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.

Authors

Katherine E. Wortley, Juan-Pablo del Rincon, Jane D. Murray, Karen Garcia, Keiji Iida, Michael O. Thorner, Mark W. Sleeman

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The GH/IGF-1 axis in 6-month-old male Ghrl–/– mice fed a standard diet o...
The GH/IGF-1 axis in 6-month-old male Ghrl–/– mice fed a standard diet or HFD 3 weeks after weaning. (A) Pituitary GH mRNA in Ghrl+/+ and Ghrl–/– mice on standard diet was similar, whereas on the HFD, GH mRNA was increased in Ghrl–/– compared with Ghrl+/+ mice (*P < 0.05). (B) IGF-1 mRNA in liver was similar in Ghrl+/+ and Ghrl–/– mice on the standard diet, whereas it showed a tendency to be increased in Ghrl–/– mice compared with Ghrl+/+ mice fed a HFD. (C) GHR mRNA in the liver of Ghrl+/+ and Ghrl–/– mice on standard diet was similar, whereas on the HFD, GHR mRNA was increased in Ghrl–/– mice compared with Ghrl+/+ mice (*P < 0.05). n = 5–9/genotype.