Differences in Acyl- and Desacyl Ghrelin Circulating Patterns in Healthy Young Men Support the Role of Duration of Food Deprivation for Ghrelin Regulation

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 676-684-Central Regulation of Appetite & Feeding
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-678
Leon S Farhy*, Ralf Nass, Jianhua Liu, Suzan S Pezzoli, Bruce D Gaylinn and Michael O Thorner
University of Virginia Health System, Charlottesville, VA
Ghrelin is a 28-amino acid gut peptide that regulates GH, appetite and metabolism. Acylation of serine3 with octanoate in the X/A-cells is required for its GH-releasing activity and orexigenic effects. The X/A-cells are thought to (co)secrete two main forms of ghrelin, acyl- and desacyl-ghrelin. Acyl-ghrelin increases before meals and at midnight, but decreases with long-term fasting (1) and is acutely inhibited by insulin (2). We have suggested that, in addition to insulin, acyl-ghrelin regulation depends also on the time elapsed from the last meal, which may cause depletion of the substrate for the enzyme GOAT (3). This is supported by our finding that a 48-hr fast increases the desacyl-to-acyl ghrelin (D/A) ratio which cannot be explained by changes in a possible acyl- to desacyl-ghrelin conversion (3). Given the potential importance of the duration of fasting for acyl-ghrelin regulation, this study examines the decline in ghrelin acylation as a function of the time elapsed since the last meal.

Subjects and Methods: Seven men, age (mean±SD) 21±2.9yr; BMI 22±2.9kg/m2 were studied on two occasions on the Clinical Research Center. Volunteers were admitted in the afternoon and ate a standardized dinner at 6 PM. At 8 AM after an overnight fast, blood was sampled every 10 min for 26 hr for acyl- and desacyl-ghrelin using an in-house two-site sandwich assay. On one (FED) admission, 3 meals were served at 8 AM, 1 PM and 6 PM. No meals were served on the other [FASTED] admission. On both admissions, 24 hr after sampling onset, breakfast was served at 8 AM. Changes in ghrelin acylation after food deprivation were assessed via changes in the D/A ratio during four 6-hr periods: P1 (8 AM-2 PM); P2 (2 PM-8 PM); P3 (8 PM-2 AM); P4 (2 AM-8AM).

Results: The D/A ratios during the FED admission were 2.2±1.85 (P3) and 3±2.39 (P4), or a 1.4-fold increase overnight (paired t-test, p=0.03). During the FASTED admission, the D/A ratios continued to increase significantly as the fast progressed (ANOVA, p=0.002): 4.6±4.44 (P1), 5.7±7.98 (P2), 6.8±6.2 (P3) and 10.4±9.29 (P4), or a 2.3 fold increase from P1 to P4.

Conclusion: These findings suggest that the decline in ghrelin acylation begins shortly after dinner and gradually continues until the next meal is ingested. They support our model-derived hypothesis (3) that the time elapsed since the last meal plays a role in acyl-ghrelin regulation under fasting conditions, and possibly under normal fed conditions, at least overnight.

(1) Liu J, Prudom CE, Nass R, Pezzoli SS, Oliveri MC, Johnson ML, Veldhuis P, Gordon DA, Howard AD, Witcher DR, Geysen HM, Gaylinn BD, Thorner MO. Novel Ghrelin Assays Provide Evidence for Independent Regulation of Ghrelin Acylation and Secretion in Healthy Young Men. J Clin Endocrinol Metab. 93(5):1980-1987, 2008. (2) Nass R, Liu J, Pezzoli SS, Gaylinn BD, Farhy LS, Thorner MO. Inhibition of Acyl-Ghrelin Release in Healthy Young Adults during Euglycemic Hyperinsulinemic Clamp 93th Annual Meeting of the Endocrine Society, Boston, 2011. (3) Farhy LS, Nass R, Liu J, Pezzoli SS, Gaylinn BD, Thorner MO. Duration Of Fasting And Inhibition By Insulin May Contribute To The In-Vivo Reduction Of Acyl-Ghrelin Release During A Short-Term Fast In Healthy Young Men   94th Annual Meeting of the Endocrine Society, Houston, 2012.

Nothing to Disclose: LSF, RN, JL, SSP, BDG, MOT

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: R01DK082805, K23RR018770, M01RR 00847, R01DK076037