Obese Subjects Respond to the Stimulatory Effect of the Ghrelin Agonist Growth Hormone-Releasing Peptide-2 on Food Intake*

Abstract

The administration of the growth hormone (GH) secretagogue GH-releasing peptide (GHRP)-2, like ghrelin, increases food intake (FI) in lean healthy men. The aim of this study was to investigate whether this effect occurs in obese subjects and whether it is dose-dependent. Nineteen subjects (10 lean and nine obese), all healthy and weight stable, received a double-blind randomized subcutaneous infusion of GHRP-2 at high dose (HD; 1 mug/kg per hour), low dose (0.1 microg/kg per hour), or placebo for 270 minutes over three study visits. Blood for hormone assays was collected through an intravenous forearm catheter. Hunger and fullness were rated on visual analog scales before and after a fixed breakfast (320 kcal at 120 minutes) and a buffet lunch at 240 minutes. Before lunch, subjects received taped instructions to eat as much as they wanted. GHRP-2 infusion significantly increased ad libitum FI in a dose-dependent manner by 10.2 +/- 3.9% at low dose (p = 0.011) and by 33.5 +/- 5.8% at HD (p = 0.000) compared with placebo. Obesity status did not influence the effect of GHRP-2 on FI. All subjects had greater ratings of appetite before but similar levels of fullness after the meal with the HD GHRP-2. Serum GH levels increased dose dependently in all subjects. The dual stimulatory effect of GHRP-2 on FI and human GH is dose dependent. Obese individuals retain their ability to respond to GHRP-2 both in terms of FI and human GH.