title: The level of circulating octanoate does not predict ghrelin O-acyl transferase (GOAT)-mediated acylation of ghrelin during fasting.
abstract: BACKGROUND
  Acyl-ghrelin is a 28-amino acid peptide released from the stomach. Ghrelin O-acyl transferase (GOAT) attaches an 8-carbon medium-chain fatty acid (MCFA) (octanoate) to serine 3 of ghrelin. This acylation is necessary for the activity of ghrelin. Animal data suggest that MCFAs provide substrate for GOAT and an increase in nutritional octanoate increases acyl-ghrelin.
  
  
  OBJECTIVE
  To address the question of the source of substrate for acylation, we studied whether the decline in ghrelin acylation during fasting is associated with a decline in circulating MCFAs.
  
  
  METHODS
  Eight healthy young men (aged 18-28 years, body mass index range, 20.6-26.2 kg/m(2)) had blood drawn every 10 minutes for acyl- and desacyl-ghrelin and every hour for free fatty acids (FFAs) during the last 24 hours of a 61.5-hour fast and during a fed day. FFAs were measured by a highly sensitive liquid chromatography-mass spectroscopy method. Acyl- and desacyl-ghrelin were measured in an in-house assay; the results were published previously. Ghrelin acylation was assessed by the ratio of acyl-ghrelin to total ghrelin.
  
  
  RESULTS
  With the exception of MCFAs C8 and C10, all other FFAs, the MCFAs (C6 and C12), and the long-chain fatty acids (C14-C18) significantly increased with fasting (P < .05). There was no significant association between the fold change in ghrelin acylation and circulating FFAs.
  
  
  CONCLUSIONS
  These results suggest that changes in circulating MCFAs are not linked to the decline in ghrelin acylation during fasting and support the hypothesis that acylation of ghrelin depends at least partially on the availability of gastroluminal MCFAs or the regulation of GOAT activity.
authors.affiliation: Division of Endocrinology and Metabolism (R.N., J.L., S.S.P., L.S.F., B.D.G., M.O.T.), Department of Medicine, Center for Diabetes Technology (L.S.F.), and Department of Health Sciences (J.P.), University of Virginia, Charlottesville, Virginia 22908; and Eli Lilly (A.N., M.H.), Lilly Research Laboratories, Indianapolis, Indiana 46285.
authors.forename: Ralf
authors.initials: R
authors.lastname: Nass
authors.forename: Alexander
authors.initials: A
authors.lastname: Nikolayev
authors.forename: Jianhua
authors.initials: J
authors.lastname: Liu
authors.forename: Suzan S
authors.initials: SS
authors.lastname: Pezzoli
authors.forename: Leon S
authors.initials: LS
authors.lastname: Farhy
authors.forename: James
authors.initials: J
authors.lastname: Patrie
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Gaylinn
authors.forename: Mark
authors.initials: M
authors.lastname: Heiman
authors.forename: Michael O
authors.initials: MO
authors.lastname: Thorner
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D002210:Caprylates / Q000097:blood*; D005215:Fasting / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D054439:Ghrelin / Q000378:metabolism*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D002210:Caprylates; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D000217:Acyltransferases; C542776:MBOAT4 protein, human; C031492:octanoic acid