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Plasma Levels of Intact and Degraded Ghrelin and Their Responses to Glucose Infusion in Anorexia Nervosa

Health Services Center (M.H.), National Graduate Institute for Policy Studies, 162-8677 Tokyo, Japan; Department of Medicine (R.O., N.H., K.T.), Institute of Clinical Endocrinology, Tokyo Women’s Medical University, School of Medicine, 162-8666 Tokyo, Japan; Department of Medicine (H.K.), Miyazaki University, School of Medicine, 889-1692 Miyazaki, Japan; and Department of Physiology (T.S.), Nippon Medical School, 113-8602 Tokyo, Japan

Address all correspondence and requests for reprints to: Mari Hotta, M.D., Health Services Center, National Graduate Institute for Policy Studies, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8677, Japan. E-mail: marihs{at}grips.ac.jp.

Octanoylated ghrelin (1–28) (intact ghrelin) is rapidly and easily degraded to desoctanoyl forms or smaller fragments (degraded ghrelin). Plasma levels of intact and degraded ghrelin were examined in 30 patients with anorexia nervosa (AN) (body mass index, 8.81–22.4 kg/m²) and 16 age-matched healthy women using several assay methods. Plasma levels of ghrelin measured using immunocomplex transfer-enzyme immunoassay, which specifically detects intact ghrelin, were lower in AN than controls. Plasma ghrelin levels in AN measured using the active ghrelin ELISA kit, which is advertised as specifically detecting intact ghrelin, did not differ significantly from controls. Plasma levels of desoctanoyl ghrelin using the desacyl-ghrelin ELISA kit, N-terminus ghrelin using the ghrelin active RIA kit, and C-terminus ghrelin using the ghrelin total RIA kit were significantly higher in AN than controls, and displayed significant negative correlations with body mass index. Plasma levels of ghrelin determined using immunocomplex transfer-enzyme immunoassay or active ghrelin ELISA during iv glucose infusion were suppressed in both AN and controls, whereas plasma levels of degraded ghrelin levels were not significantly decreased in AN. Plasma levels of intact ghrelin are therefore not higher in AN than controls, whereas degraded forms of ghrelin are elevated in AN. Rapid suppression of plasma intact ghrelin, but not degraded ghrelin, occurs in AN in response to glucose infusion. The profiles of intact and degraded forms of ghrelin in plasma of AN patients differ from those of healthy women.

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