Postprandial Total Ghrelin Suppression Is Modulated by Melanocortin Signaling in Humans

Abstract

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