Ghrelin Induces Adiposity in Rodents

Nature. 2000 Oct 19;407(6806):908-13. doi: 10.1038/35038090.

Abstract

The discovery of the peptide hormone ghrelin, an endogenous ligand for the growth hormone secretagogue (GHS) receptor, yielded the surprising result that the principal site of ghrelin synthesis is the stomach and not the hypothalamus. Although ghrelin is likely to regulate pituitary growth hormone (GH) secretion along with GH-releasing hormone and somatostatin, GHS receptors have also been identified on hypothalamic neurons and in the brainstem. 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.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Animals
  • Circadian Rhythm
  • Energy Metabolism
  • Fasting
  • Food
  • Ghrelin
  • Growth Hormone / metabolism
  • Hypothalamus / drug effects
  • Hypothalamus / physiology
  • Injections, Intraventricular
  • Male
  • Mice
  • Peptide Hormones*
  • Peptides / administration & dosage
  • Peptides / blood
  • Peptides / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / blood
  • Receptors, Cell Surface / physiology
  • Receptors, G-Protein-Coupled*
  • Receptors, Ghrelin
  • Weight Gain / drug effects
  • Weight Gain / physiology*

Substances

  • Ghrelin
  • Peptide Hormones
  • Peptides
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Receptors, Ghrelin
  • Growth Hormone