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Postprandial Suppression of Plasma Ghrelin Level Is Proportional to Ingested Caloric Load but Does Not Predict Intermeal Interval in Humans

University of Washington School of Medicine (H.S.C., D.E.C., M.S.P., P.A.B., C.C.M., D.S.W.) Seattle, Washington 98195; Veterans Affairs Puget Sound Health Care System (D.E.C.), Seattle, Washington 98108; and Harborview Medical Center (P.A.B., D.S.W.), Seattle, Washington 98104

Address all correspondence and requests for reprints to: David S. Weigle, M.D., Endocrinology, Box 359757, Harborview Medical Center, 325 Ninth Avenue, Seattle, Washington 98104. E-mail: weigle{at}u.washington.edu.

Plasma ghrelin levels rise before meals and fall rapidly afterward. If ghrelin is a physiological meal-initiation signal, then a large oral caloric load should suppress ghrelin levels more than a small caloric load, and the request for a subsequent meal should be predicted by recovery of the plasma ghrelin level. To test this hypothesis, 10 volunteers were given, at three separate sessions, liquid meals (preloads) with widely varied caloric content (7.5%, 16%, or 33% of total daily energy expenditure) but equivalent volume. Preloads were consumed at 0900 h, and blood was sampled every 20 min from 0800 h until 80 min after subjects spontaneously requested a meal. The mean (± SE) intervals between ingestion of the 7.5%, 16%, and 33% preloads and the subsequent voluntary meal requests were 247 ± 24, 286 ± 20, and 321 ± 27 min, respectively (P = 0.015), and the nadir plasma ghrelin levels were 80.2 ± 2.8%, 72.7 ± 2.7%, and 60.8 ± 2.7% of baseline (the 0900 h value), respectively (P < 0.001). A Cox regression analysis failed to show a relationship between ghrelin profile and the spontaneous meal request. We conclude that the depth of postprandial ghrelin suppression is proportional to ingested caloric load but that recovery of plasma ghrelin is not a critical determinant of intermeal interval.

This work was supported by individual grants from the National Institutes of Health (DK55460, DK02860, and DK61516), a General Clinical Research Center grant (RR00037), a Clinical Nutrition Research Unit grant (DK35816), a Diabetes Endocrinology Research Center grant (DK17047), a Burroughs Wellcome Fund Career Award (no. 233 to D.E.C.), and the Medical Research Service of the Department of Veterans Affairs.

Abbreviations: AUC, Area under the curve; GCRC, General Clinical Research Center.

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