Postprandial total ghrelin suppression is modulated by melanocortin signaling in humans

J Clin Endocrinol Metab. 2013 Feb;98(2):E288-92. doi: 10.1210/jc.2012-2553. Epub 2013 Jan 11.


Contents: Ghrelin is implicated in meal initiation because circulating levels increase before and fall after meal consumption. In rodents, ghrelin stimulates food intake via hypothalamic circuits expressing the melanocortin 4 receptor (MC4R).

Objective: The aim of the study was to investigate the impact of central melanocortinergic tone on ghrelin secretion in humans. DESIGN/SETTING/PATIENTS/MAIN OUTCOME MEASURE: We measured plasma total ghrelin before and after 3 standardized meals in patients with MC4R mutations and obese and lean controls. Fasting total ghrelin, area under the curve, and early (30-min) and intermeal postprandial total ghrelin suppression (the percentage difference between the premeal and the 30-min postprandial or intermeal nadir total ghrelin concentration) were calculated.

Results: Fasting total ghrelin concentrations and area under the curve for total ghrelin concentrations were significantly decreased in both obese groups compared to lean controls (fasting total ghrelin: lean controls, 1083 ± 203 pg/ml; and obese controls, 696 ± 81 pg/ml; MC4R: 609 ± 99 pg/ml, P < .05). Early and intermeal postprandial total ghrelin suppression was attenuated in MC4R-deficient patients compared to lean controls (P < .05); a similar pattern was observed for early postprandial suppression in comparison with obese controls, but this difference did not reach statistical significance (P = .09).

Conclusions: These findings are consistent with a role for central melanocortinergic signaling in modulating meal-related total ghrelin suppression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Fasting / blood*
  • Female
  • Ghrelin / blood*
  • Humans
  • Insulin / blood
  • Male
  • Mutation
  • Obesity / blood
  • Obesity / genetics
  • Obesity / metabolism*
  • Postprandial Period / physiology*
  • Receptor, Melanocortin, Type 4 / genetics*
  • Receptor, Melanocortin, Type 4 / metabolism


  • Blood Glucose
  • Ghrelin
  • Insulin
  • Receptor, Melanocortin, Type 4