Weight loss increases circulating levels of ghrelin in human obesity

OBJECTIVE: Ghrelin, a novel endogenous ligand for the GH secretagogue receptor, has been reported to have adipogenic actions and induce weight gain in addition to its GH-releasing properties. Interestingly, recent data indicate that ghrelin is downregulated in human obesity, which is also known to be accompanied by reduced GH levels. PATIENTS AND METHODS: To investigate the influence of weight loss on circulating levels of ghrelin we recruited eight obese women among patients attending a 6-month weight-loss course organized by The Danish Heart Association. We measured body composition including computerized tomography as well as fasting plasma ghrelin concentrations before and after weight loss. RESULTS: Plasma ghrelin concentrations increased by 12% following weight loss (P < 0.01), and the increase in ghrelin levels was positively correlated with the extent of weight loss (r = 0.68, P < 0.05). Exposure to exogenous GH intravenously did not influence fasting ghrelin levels either before or after weight loss. Our data further suggest the existence of hyperghrelinaemia in a single subject with long-standing obesity but no signs of GH excess. CONCLUSIONS: This study provides evidence of a reversible suppression of ghrelin associated with obesity. The feasibility of measuring ghrelin in the circulation provides a new tool for the investigation of the complex hormonal regulation of appetite and energy balance.