TY - JOUR
T1 - Postprandial total ghrelin suppression is modulated by melanocortin signaling in humans
AU - Van Der Klaauw, Agatha A.
AU - Keogh, Julia M.
AU - Henning, Elana
AU - Blackwood, Anthea
AU - Haqq, Andrea M.
AU - Purnell, Jonathan Q.
AU - Farooqi, I. Sadaf
PY - 2013/2
Y1 - 2013/2
N2 - 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 MC4Rdeficient 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.
AB - 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 MC4Rdeficient 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.
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U2 - 10.1210/jc.2012-2553
DO - 10.1210/jc.2012-2553
M3 - Article
C2 - 23316086
AN - SCOPUS:84873672056
SN - 0021-972X
VL - 98
SP - E288-E292
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 2
ER -