Ghrelin induces adiposity in rodents

Abstract

The discovery of the peptide hormone ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor1,2, yielded the surprising result3 that the principal site of ghrelin synthesis is the stomach and not the hypothalamus. Although ghrelin is likely to regulate pituitary growth hormone (GH) secretion3,4 along with GH-releasing hormone and somatostatin, GHS receptors have also been identified on hypothalamic neurons5 and in the brainstem6. Apart from potential paracrine effects, ghrelin may thus offer an endocrine link between stomach, hypothalamus and pituitary, suggesting an involvement in regulation of energy balance. Here we show that peripheral daily administration of ghrelin caused weight gain by reducing fat utilization in mice and rats. Intracerebroventricular administration of ghrelin generated a dose-dependent increase in food intake and body weight. Rat serum ghrelin concentrations were increased by fasting and were reduced by re-feeding or oral glucose administration, but not by water ingestion. We propose that ghrelin, in addition to its role in regulating GH secretion, signals the hypothalamus when an increase in metabolic efficiency is necessary.

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Figure 1: Ghrelin-stimulated adiposity in mice.
Figure 2: Differential effects of ghrelin and growth hormone on respiratory quotient (RQ) and energy expenditure (EE) in mice.
Figure 3: Ghrelin induced a positive energy balance in dwarf rats deficient in growth hormone.
Figure 4: Central effects of ghrelin on energy balance in adult male Sprague–Dawley rats.
Figure 5: Circulating ghrelin levels respond to feeding state in adult male Sprague–Dawley rats.

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Acknowledgements

We thank J. Caro, G. Cutler Jr, E. Ravussin, R. Al-Awar, C.J. Strasburger and A. Tashjian Jr for critical review, R. Palmiter for providing NPY-deficient mice and L. Craft, J. Baker, J. Bridwell, J. Jacobs, W.T. Johnson, P. Surface, F. Tinsley and T. Butler for technical assistance.

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Correspondence to Matthias Tschöp.

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Tschöp, M., Smiley, D. & Heiman, M. Ghrelin induces adiposity in rodents. Nature 407, 908–913 (2000). https://doi.org/10.1038/35038090

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