Subcutaneous administration of ghrelin stimulates energy intake in healthy lean human volunteers

Abstract

Background: The gastric hormone ghrelin appears a useful agent to stimulate food intake in people with anorexia of illness. The loss of ghrelin's acyl group renders it inactive, thus it has been thought that subcutaneous administration may be problematic. Objective: To investigate whether human subjects are sensitive to the effects of ghrelin administered by single subcutaneous injection. Study design: Randomized, double-blind, placebo-controlled trial. Subjects: Sixteen healthy lean volunteers (eight men and eight women). Protocol: Fasted subjects received subcutaneous injections of ghrelin (3.6 nmol/kg) or saline. After 30 min, a buffet breakfast was served. Results: Ghrelin injection increased energy intake by 27% (ghrelin 50767691 kJ versus saline 42307607 kJ, P ¼ 0.04). Ghrelin appeared to enhance the perceived palatability of the food offered (palatability score: ghrelin 81.173.6 versus saline 70.074.4; P ¼ 0.03). Conclusions: These results suggest that subcutaneous ghrelin is effective at stimulating energy intake and improving palatability and may be of direct use in the treatment of appetite loss.

Opioid-Dependent Anticipatory Negative Contrast and Binge-Like Eating in Rats with Limited Access to Highly Preferred Food

“…Unlike leptin, ghrelin, a 28-residue, post-translationally acylated, endogenous ligand of the GH secretagogue receptor (GHSR1a), is a predominantly stomach-derived, anabolic hormone whose circulating levels are homeostatically increased by energy insufficiency to signal the central nervous system. Given pharmacologically, the Ser 3 -n-octanoylated form of ghrelin is orexigenic and decreases energy expenditure and utilization of fat as an energy substrate, leading to weight gain and adiposity with chronic central administration (Druce et al, 2006;Tschop et al, 2000;Wortley et al, 2005). Because leptin and ghrelin respectively increased and decreased in chow/preferred-fed rats, obesity and feeding adaptations probably developed despite energy balance-appropriate, homeostatic accommodations to levels of both hormones (similar to diet-induced human obesity), rather than because of dysregulated release.…”

The role of the central ghrelin system in reward from food and chemical drugs

“…For a review on this topic, we refer the reader to Skibicka and Dickson 2011. In normal weight healthy volunteers, ghrelin has been shown to increase hunger scores, to enhance food palatability and to increase caloric intake in a free-feeding buffet situation (Cummings et al 2004;Druce et al 2006;. One recent study of food economics reported that ghrelin even increases the amount of money an individual is prepared to pay for individual food items (Tang et al 2011).…”

Safety, tolerability and pharmacokinetics of intravenous ghrelin for cancer-related anorexia/cachexia: a randomised, placebo-controlled, double-blind, double-crossover study

“…(Nagaya et al, 2001a;Wren et al, 2001;Akamizu et al, 2004;Schmid et al, 2005;Levin et al, 2006) or subcutaneous (Enomoto et al, 2003;Druce et al, 2006) ghrelin showed safety and tolerability at dosages up to 10 mg kg À1 -sufficient to promote orexigenic, prokinetic, and GH-releasing effects; in those studies, a sensation of warmth, sleepiness, bowel movements, and hunger were reported. Comparable results with i.v.…”