Weight gain decreases elevated plasma ghrelin concentrations of patients with anorexia nervosa

Medical Department, Innenstadt, University Hospital, Ziemssenstrasse 1, D-80336 Munich, Germany. botto@medinn.med.uni-muenchen.de

OBJECTIVE: Ghrelin is a new gastric hormone that has been identified as an endogenous ligand for the growth hormone (GH) secretagogue receptor subtype 1a (GHS-R1a). Ghrelin administration however not only stimulates GH secretion but also induces adiposity in rodents by increasing food intake and decreasing fat utilization. We hypothesized that impaired ghrelin secretion in anorexia nervosa may be involved in the pathogenesis of this eating disorder. To examine this hypothesis and to further investigate the role for ghrelin in regulating energy homeostasis, we analyzed circulating ghrelin levels in patients with anorexia nervosa and examined possible correlations with clinical parameters before and after weight gain. METHODS: Plasma ghrelin levels were measured in overnight fasting plasma samples from 36 female patients with anorexia nervosa (age: 25.0+/-1.2 years, BMI: 15.2+/-0.2 kg/m(2)) before and after weight gain following psychotherapeutic treatment intervention in a psychosomatic institution. Plasma ghrelin levels were also measured in fasting plasma samples from 24 age-matched female controls (31+/-1.4 years, BMI: 22.9+/-0.45 kg/m(2)). For quantification of ghrelin levels a commercially available radioimmunoassay (Phoenix Pharmaceuticals, USA) was used. RESULTS: Fasting plasma ghrelin levels in anorectic patients were significantly higher (1057+/-95 pg/ml) than in normal age-matched female controls (514+/-63 pg/ml n=24, P=0.02). Therapeutic intervention in a psychosomatic institution caused an BMI increase of 14% (P<0.001) leading to a significant decrease in circulating ghrelin levels of 25%, (P=0.001). A significant negative correlation between Deltaghrelin and DeltaBMI was observed (correlation coefficient: -0.47, P=0.005, n=36). CONCLUSION: We show for the first time that fasting plasma levels of the novel appetite-modulating hormone ghrelin are elevated in anorexia nervosa and return to normal levels after partial weight recovery. These observations suggest the possible existence of ghrelin resistance in cachectic states such as caused by eating disorders. Future studies are necessary to investigate putative mechanisms of ghrelin resistance such as a possible impairment of intracellular ghrelin receptor signaling in pathophysiological states presenting with cachexia.

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				A. L. Barkan, E. V. Dimaraki, S. K. Jessup, K. V. Symons, M. Ermolenko, and C. A. Jaffe Ghrelin Secretion in Humans Is Sexually Dimorphic, Suppressed by Somatostatin, and Not Affected by the Ambient Growth Hormone Levels J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2180 - 2184. [Abstract] [Full Text] [PDF]

				D. S. Weigle, D. E. Cummings, P. D. Newby, P. A. Breen, R. S. Frayo, C. C. Matthys, H. S. Callahan, and J. Q. Purnell Roles of Leptin and Ghrelin in the Loss of Body Weight Caused by a Low Fat, High Carbohydrate Diet J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1577 - 1586. [Abstract] [Full Text] [PDF]

				D. E. Cummings and M. H. Shannon Roles for Ghrelin in the Regulation of Appetite and Body Weight Arch Surg, April 1, 2003; 138(4): 389 - 396. [Full Text] [PDF]

				D. Yasuhara, T. Naruo, N. Nagai, M. Tanaka, T. Muranaga, and S.-i. Nozoe Insulinogenic index at 15 min as a marker of nutritional rehabilitation in anorexia nervosa Am. J. Clinical Nutrition, February 1, 2003; 77(2): 292 - 299. [Abstract] [Full Text] [PDF]

				A. L. D. Riis, T. K. Hansen, N. Moller, J. Weeke, and J. O. L. Jorgensen Hyperthyroidism Is Associated with Suppressed Circulating Ghrelin Levels J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 853 - 857. [Abstract] [Full Text] [PDF]

				V. Tolle, M. Kadem, M.-T. Bluet-Pajot, D. Frere, C. Foulon, C. Bossu, R. Dardennes, C. Mounier, P. Zizzari, F. Lang, et al. Balance in Ghrelin and Leptin Plasma Levels in Anorexia Nervosa Patients and Constitutionally Thin Women J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 109 - 116. [Abstract] [Full Text] [PDF]

				G. Schaller, A. Schmidt, J. Pleiner, W. Woloszczuk, M. Wolzt, and A. Luger Plasma Ghrelin Concentrations Are Not Regulated by Glucose or Insulin: A Double-Blind, Placebo-Controlled Crossover Clamp Study Diabetes, January 1, 2003; 52(1): 16 - 20. [Abstract] [Full Text] [PDF]

				H. Hosoda, M. Kojima, and K. Kangawa Ghrelin and the Regulation of Food Intake and Energy Balance Mol. Interv., December 1, 2002; 2(8): 494 - 503. [Abstract] [Full Text]

				A. DelParigi, M. Tschop, M. L. Heiman, A. D. Salbe, B. Vozarova, S. M. Sell, J. C. Bunt, and P. A. Tataranni High Circulating Ghrelin: A Potential Cause for Hyperphagia and Obesity in Prader-Willi Syndrome J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5461 - 5464. [Abstract] [Full Text] [PDF]

				U. Pagotto, A. Gambineri, V. Vicennati, M. L. Heiman, M. Tschop, and R. Pasquali Plasma Ghrelin, Obesity, and the Polycystic Ovary Syndrome: Correlation with Insulin Resistance and Androgen Levels J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5625 - 5629. [Abstract] [Full Text] [PDF]

				F. Rubino, M. Gagner, M. Camilleri, F. Cremonini, A. Geliebter, D. E. Cummings, J. Q. Purnell, and D. S. Weigle Weight Loss and Plasma Ghrelin Levels N. Engl. J. Med., October 24, 2002; 347(17): 1379 - 1381. [Full Text] [PDF]

				C. Schofl, R. Horn, T. Schill, H. W. Schlosser, M. J. Muller, and G. Brabant Circulating Ghrelin Levels in Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4607 - 4610. [Abstract] [Full Text] [PDF]

				H. Ariyasu, K. Takaya, H. Hosoda, H. Iwakura, K. Ebihara, K. Mori, Y. Ogawa, K. Hosoda, T. Akamizu, M. Kojima, et al. Delayed Short-Term Secretory Regulation of Ghrelin in Obese Animals: Evidenced by a Specific RIA for the Active Form of Ghrelin Endocrinology, September 1, 2002; 143(9): 3341 - 3350. [Abstract] [Full Text] [PDF]