Ingested medium-chain fatty acids are directly utilized for the acyl modification of ghrelin.
Ghrelin, an acylated brain and gut peptide, is primarily produced by endocrine cells of the gastric mucosa for secretion into the circulation. The major active form of ghrelin is a 28-amino-acid peptide containing an n-octanoyl modification at serine that is essential for activity. Studies have identified multiple physiological functions for ghrelin, including GH release, appetite stimulation, and metabolic fuel preference. Until now, there has not been any report detailing the mechanism of ghrelin acyl modification. Here we report that ingestion of either medium-chain fatty acids (MCFAs) or medium-chain triacylglycerols (MCTs) increased the stomach concentrations of acylated ghrelin without changing the total (acyl- and des-acyl-) ghrelin amounts. After ingestion of either MCFAs or MCTs, the carbon chain lengths of the acyl groups attached to nascent ghrelin molecules corresponded to that of the ingested MCFAs or MCTs. Ghrelin peptides modified with n-butyryl or n-palmitoyl groups, however, could not be detected after ingestion of the corresponding short-chain or long-chain fatty acids, respectively. Moreover, n-heptanoyl ghrelin, an unnatural form of ghrelin, could be detected in the stomach of mice after ingestion of either n-heptanoic acid or glyceryl triheptanoate. These findings indicate that ingested medium-chain fatty acids are directly used for the acylation of ghrelin.
Nishi
Yoshihiro
Y
Department of Molecular Genetics, Institute of Life Science, Kurume University, Kurume-city, Fukuoka 839-0861, Japan. nishi@lsi.kurume-u.ac.jp
Hiejima
Hiroshi
H
Hosoda
Hiroshi
H
Kaiya
Hiroyuki
H
Mori
Kenji
K
Fukue
Yoshihiko
Y
Yanase
Toshihiko
T
Nawata
Hajime
H
Kangawa
Kenji
K
Kojima
Masayasu
M
D000215:Acylation; D000818:Animals; D002208:Caproates / Q000008:administration & dosage / Q000378:metabolism; D002210:Caprylates / Q000008:administration & dosage / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D005227:Fatty Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism; D054439:Ghrelin; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000378:metabolism; D007700:Kinetics; D007850:Lauric Acids / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019308:Palmitic Acid / Q000008:administration & dosage / Q000378:metabolism; D036361:Peptide Hormones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D013329:Structure-Activity Relationship; D014280:Triglycerides / Q000008:administration & dosage / Q000378:metabolism
D002208:Caproates; D002210:Caprylates; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D006538:Heptanoic Acids; D007850:Lauric Acids; D036361:Peptide Hormones; D012333:RNA, Messenger; D014280:Triglycerides; C030358:lauric acid; C037652:hexanoic acid; D019308:Palmitic Acid; C031492:octanoic acid