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.
Address correspondence and reprint requests to Matthias Tschöp, Lilly Research Laboratories, Eli Lilly and Company Corporate Center, Drop 0545, Indianapolis, IN 46285. E-mail:.
M.L.H. and V.D. are employed by and hold stock in Eli Lilly. M.H.T. is a temporary (postdoctoral) employee of Eli Lilly.
Received for publication 7 December 2000 and accepted 22 January 2001. Posted on the World Wide Web at www.diabetes.org/diabetes on 23 February 2001.