Increased lipolysis after infusion of acylated ghrelin: a randomized, double‐blinded placebo‐controlled trial in hypopituitary patients

Abstract

Acylated ghrelin increases growth hormone (GH) and adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland. Additionally, it increases free fatty acid levels independently of GH and ACTH, but the impact of ghrelin on fatty acid turnover has not been determined. This study was designed to test whether acylated ghrelin directly increases the turnover rate of fatty acids. Eight hypopituitary patients on stable replacement with GH and hydrocortisone were included in a randomized, double-blinded, placebo-controlled crossover study including two study days: (a) infusion of acylated ghrelin and (b) infusion of saline. The study day comprised a basal period (t=0-120minutes) and a hyperinsulinaemic-euglycemic clamp period (t=120-300minutes). Whole-body lipolysis was estimated at t=90-120 and t=270-300minutes with a palmitate isotope dilution technique. Infusion of acylated ghrelin resulted in 10 times increased total ghrelin area under the curve (AUC) levels in the basal period and 15 times increased AUC levels in the clamp period compared with saline infusion (P<.001). GHAUC levels were largely unaffected by ghrelin compared to saline infusion during both the basal and clamp period, but cortisolAUC levels increased by 15% after ghrelin compared to saline infusion in the basal period (P=.03). Palmitate turnover was increased by 43% in the basal period (difference: 77 (20) µmol/min, P=.01) and unchanged in the clamp period (difference 0.9 (17) µmol/min, P=1.0) after ghrelin compared to saline infusion. Our results support the hypothesis that pharmacological levels of acylated ghrelin directly activate lipolysis at the whole-body level.