Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects

Objective: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. Design: A randomized, double-blind, placebo-controlled study. Patients: Nine lean subjects (mean body mass index (BMI) 23.5 +/- 3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4 +/- 10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4 +/- 1.0 kg/m(2)). Interventions: Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. Main outcome measures: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. Results: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P = 0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). Conclusions: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.