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Balance in Ghrelin and Leptin Plasma Levels in Anorexia Nervosa Patients and Constitutionally Thin Women

INSERM, U-549 (V.T., M.T.B.P., C.F., R.D., P.Z., J.E.), and Clinique des Maladies Mentales et de l’Encéphale (C.F., R.D.), 75014 Paris, France; and Services d’Endocrinologie et de Psychiatrie (M.K., D.F., C.B., C.M., F.L., B.E.), Hôpital de Bellevue, 42100 Saint Etienne, France

Address all correspondence and requests for reprints to: Dr. Jacques Epelbaum, INSERM, U-549, IFR Broca-Sainte Anne, 2 ter rue d’Alésia, 75014 Paris, France. E-mail: epelbaum{at}broca.inserm.fr.

Ghrelin, a 28-amino acid octanoylated peptide, has recently been identified in rat stomach as an endogenous ligand for the GH secretagogue receptor. In addition to GH-releasing properties, exogenous ghrelin injections exert orexigenic effects in both rodents and humans. As the endogenous peptide appears directly related to feeding behavior, we assessed its plasma levels in anorexia nervosa (AN) patients before and after renutrition and in constitutionally thin subjects with body mass indexes (BMIs) equivalent to those of AN women but with no abnormal feeding behavior. The relationships between plasma ghrelin levels and other neuroendocrine and nutritional parameters, such as GH, leptin, T₃, and cortisol, were also investigated. In AN patients, morning fasting plasma ghrelin levels were doubled compared with levels in controls, constitutionally thin subjects, and AN patients after renutrition. Twenty-four-hour plasma ghrelin, GH, and cortisol levels determined every 4 h were significantly increased, whereas 24-h plasma leptin levels were decreased in AN patients compared with controls and constitutionally thin subjects. Both plasma ghrelin and leptin levels returned to control values in AN patients after renutrition. Constitutionally thin subjects displayed intermediate 24-h plasma ghrelin and leptin levels, significantly different from controls and AN patients, whereas GH and cortisol were not modified. Ghrelin was negatively correlated with BMI, leptin, and T₃ in controls, constitutionally thin subjects, and AN patients, whereas no correlation was found between GH and ghrelin or between cortisol and ghrelin. Ghrelin and BMI or T₃ were still correlated after renutrition, suggesting that ghrelin is also a good nutritional indicator. Basal and GHRH-stimulated GH release were significantly increased in AN patients only. In conclusion, ghrelin is increased in AN and constitutionally thin subjects who display very low BMI but different eating behaviors, suggesting that not only is ghrelin dependent on body fat mass, but it is also influenced by nutritional status. Even though endogenous ghrelin is not strictly correlated with basal GH secretion, it may be involved in the magnitude of GHRH-induced GH release in AN patients.

This work was supported by INSERM and its ATC Nutrition Section.

Abbreviations: AN, Anorexia nervosa; AUC, area under the curve; BMI, body mass index; GHS, GH secretagogue; GHS-R, GH secretagogue receptor.

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