Developmental changes in the pattern of ghrelin's acyl modification and the levels of acyl-modified ghrelins in murine stomach.
Ghrelin is an acylated peptide hormone secreted primarily from endocrine cells in the stomach. The major active form of ghrelin is a 28-amino acid peptide with an n-octanoyl modification at Ser(3) (n-octanoyl ghrelin), which is essential for its activity. In addition to n-octanoyl ghrelin, other forms of ghrelin peptide exist, including des-acyl ghrelin, which lacks an acyl modification, and other minor acylated ghrelin species, such as n-decanoyl ghrelin, whose Ser(3) residue is modified by n-decanoic acid. Multiple reports have identified various physiological functions of ghrelin. However, until now, there have been no reports that explore the process of ghrelin acyl modification, and only a few studies have compared the levels of des-acyl, n-octanoyl, and/or other minor populations of acylated ghrelin peptides. In this study we report that the amount of n-octanoyl ghrelin in murine stomachs increases gradually during the suckling period to a maximal level at 3 wk of age and falls sharply after the initiation of weaning. However, the concentration (picomoles per milligram of wet weight tissue) of total ghrelin, which includes des-acyl and all acylated forms of ghrelin peptides with intact C termini in murine stomach, remains unchanged across this suckling-weaning transition. Prematurely weaned mice exhibited a significant decrease in the amount of n-octanoyl or n-decanoyl ghrelin in the stomach. Orally ingested glyceryl trioctanoate, a medium-chain triacylglyceride rich in milk lipids, significantly increased the level of n-octanoyl-modified ghrelin in murine stomach. Fluctuations in the proportion of this biologically active, acyl-modified ghrelin could contribute to or be influenced by the change in energy metabolism during the suckling-weaning transition.
Nishi
Yoshihiro
Y
Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0861, Japan.
Hiejima
Hiroshi
H
Mifune
Hiroharu
H
Sato
Takahiro
T
Kangawa
Kenji
K
Kojima
Masayasu
M
D000215:Acylation; D000367:Age Factors; D000818:Animals; D000833:Animals, Suckling; D004041:Dietary Fats / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology; D005753:Gastric Mucosa / Q000378:metabolism*; D054439:Ghrelin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008892:Milk; D036361:Peptide Hormones / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000254:growth & development*; D014280:Triglycerides / Q000378:metabolism; D014886:Weaning
D004041:Dietary Fats; D054439:Ghrelin; D036361:Peptide Hormones; D014280:Triglycerides; C422650:ghrelin, des-n-octanoyl