Circulating Ghrelin Levels Are Decreased in Human Obesity

TLDR

Ghrelin, a ligand for the growth hormone secretagogue receptor, was isolated from rat stomach and is known to stimulate growth hormone secretion and promote weight gain by increasing food intake and reducing fat utilization in rodents. The study aimed to determine whether ghrelin contributes to human obesity by measuring body composition and fasting plasma ghrelin levels in Caucasian and Pima Indian subjects. Body composition was assessed by dual‑energy X‑ray absorptiometry and fasting plasma ghrelin was quantified using a radioimmunoassay in 15 Caucasians and 15 Pima Indians. Fasting plasma ghrelin was inversely correlated with body fat, insulin, and leptin, and was lower in obese Caucasians and in Pima Indians compared to lean Caucasians, with no association to height and unchanged after insulin adjustment.

Abstract

Ghrelin is a novel endogenous natural ligand for the growth hormone (GH) secretagogue receptor that has recently been isolated from the rat stomach. Ghrelin administration stimulates GH secretion but also causes weight gain by increasing food intake and reducing fat utilization in rodents. To investigate the possible involvement of ghrelin in the pathogenesis of human obesity, we measured body composition (by dual X-ray absorption) as well as fasting plasma ghrelin concentrations (radioimmunoassay) in 15 Caucasians (8 men and 7 women, 31 ± 9 years of age, 92 ± 24 kg body wt, and 29±10% body fat, mean ± SD) and 15 Pima Indians (8 men and 7 women, 33 ± 5 years of age, 97 ± 29 kg body wt, and 30 ± 8% body fat). Fasting plasma ghrelin was negatively correlated with percent body fat (r = –0.45; P = 0.01), fasting insulin (r = – 0.45; P = 0.01) and leptin (r = –0.38; P = 0.03) concentrations. Plasma ghrelin concentration was decreased in obese Caucasians as compared with lean Caucasians (P < 0.01). Also, fasting plasma ghrelin was lower in Pima Indians, a population with a very high prevalence of obesity, compared with Caucasians (87 ± 28 vs. 129 ± 34 fmol/ml; P < 0.01). This result did not change after adjustment for fasting plasma insulin concentration. There was no correlation between fasting plasma ghrelin and height. Prospective clinical studies are now needed to establish the role of ghrelin in the pathogenesis of human obesity.