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Neuroendocrine and Metabolic Effects of Acute Ghrelin Administration in Human Obesity

Division of Endocrinology and Metabolism (F.T., S.D., S.R., A.B., C.G., F.P., R.R., E.G., M.M.), Department of Internal Medicine, University of Turin, 10126 Turin, Italy; and Division of Endocrinology and Metabolism (F.B., C.G., A.J.v.d.L.), Department of Internal Medicine, Erasmus University, 3015 Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: E. Ghigo, M.D., Department of Internal Medicine, Division of Endocrinology. Corso Dogliotti 14, 10126 Torino, Italy. E-mail: ezio.ghigo{at}unito.it.

Ghrelin stimulates appetite and plays a role in the neuroendocrine response to energy balance variations. Ghrelin levels are inversely associated with body mass index (BMI), increased by fasting and decreased by food intake, glucose load, insulin, and somatostatin. Ghrelin levels are reduced in obesity, a condition of hyperinsulinism, reduced GH secretion, and hypothalamus-pituitary-adrenal axis hyperactivity. We studied the endocrine and metabolic response to acute ghrelin administration (1.0 µg/kg iv) in nine obese women [OB; BMI (mean ± SD) 36.3 ± 2.3 kg/m²] and seven normal women (NW; BMI 20.3 ± 1.7 kg/m²). Basal ghrelin levels in NW were higher than in OB (P < 0.05). In NW, ghrelin increased (P < 0.05) GH, prolactin (PRL), ACTH, cortisol, and glucose levels but did not modify insulin. In OB, ghrelin increased (P < 0.01) GH, PRL, ACTH, and cortisol levels. The GH response to ghrelin in OB was 55% lower (P < 0.02) than in NW, whereas the PRL, ACTH, and cortisol responses were similar. In OB, ghrelin increased glucose and reduced insulin (P < 0.05). Thus, obesity shows remarkable reduction of the somatotroph responsiveness to ghrelin, suggesting that ghrelin hyposecretion unlikely explains the impairment of somatotroph function in obesity. On the other hand, in obesity ghrelin shows preserved influence on PRL, ACTH, and insulin secretion as well as in glucose levels.

This work was supported by Ministero dell’Università e della Ricerca Scientifica e Tecnologica, University of Turin, Eureka (Peptido project 1923), Fondazione per lo Studio delle Malattie Endocrino Metaboliche (FSMEM), and Europeptides.

Abbreviations: AUC, Area under curve; AVP, arginine vasopressin; BMI, body mass index; GHS, GH secretagogue; GHS-R, GHS receptor; HPA, hypothalamus-pituitary-adrenal axis; IRMA, immunoradiometric assay; NW, normal women; OB, women with visceral obesity; PRL, prolactin.

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