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Predictors of Postabsorptive Ghrelin Secretion after Intake of Different Macronutrients

Division of General Medicine (P.M., G.S., B.V., A.T., A.L.) and Laboratory of Molecular Biology (G.E.W., S.M., A.M.D.B.), Ospedale San Giuseppe, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Auxologico Italiano, 28921 Verbania, Italy; and Metabolism and Nutrition Unit (A.C.), San Raffaele Scientific Institute, 20132 Milan, Italy

Address all correspondence and requests for reprints to: Paolo Marzullo, M.D., Ph.D., General Medicine, Ospedale San Giuseppe, Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Auxologico Italiano, Casella Postale 1, I-28921 Verbania, Italy. E-mail: marzullop{at}yahoo.com.

Context: Release of ghrelin, a gastrointestinal hormone regulating feeding and energy balance, is blunted in obesity, a condition associated with insulin resistance.

Objective: The objective was to identify anthropometric and metabolic predictors of postabsorptive ghrelin secretion.

Design: We evaluated ghrelin, insulin, glucose, and leptin secretion overnight and after intake of different macronutrients.

Subjects: Ten obese subjects (age, 31.8 ± 2.5 yr; body mass index, 43.4 ± 0.8 kg/m²) and six lean subjects (age, 33.5 ± 2.4 yr; body mass index, 21.8 ± 1.4 kg/m²) participated in the study.

Main Outcome Measures: The main outcome measures were resting energy expenditure (REE); fat mass; nighttime approximate entropy (ApEn) and synchronicity (cross-ApEn) of ghrelin, insulin, and leptin; insulin sensitivity by homeostatic model approach insulin-sensitivity (HOMA-S%); postabsorptive area under the curve (AUC); and of ghrelin, insulin, glucose, and leptin after carbohydrate-, lipid-, and protein-rich test meals.

Results: Nighttime ApEn scores were higher in obese than lean subjects (P < 0.01). Cross-ApEn revealed a synchronicity between ghrelin-insulin, ghrelin-leptin, and insulin-leptin in both groups. Compared with baseline, ghrelin decreased significantly (P < 0.01) in lean and obese subjects after carbohydrates (42.2 vs. 28.5%; P < 0.05), lipids (40.2 vs. 26.2%; P < 0.01), and proteins (42.2 vs. 26.3%; P < 0.01) devoid of between-meal ghrelin differences. Significant associations occurred between nocturnal ghrelin ApEn and insulin (r = 0.53; P < 0.05), postmeal ghrelin AUCs and REE (r = –0.57; P < 0.05), and HOMA-S% (r = 0.52; P < 0.05), postmeal ghrelin and HOMA-S% (r = 0.60; P < 0.05). REE (ß = –0.57; P = 0.02) and ghrelin ApEn (ß = –0.62; P = 0.01) were predictors of postmeal ghrelin AUC and , respectively.

Conclusions: Obesity determined a decreased orderliness of ghrelin secretion and a relative loss of ghrelin-insulin synchrony. Postabsorptive ghrelin secretion decreased significantly both in obese and lean subjects, was related to insulin sensitivity, and was predicted by energy expenditure and hormone pulsatility.

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