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Endocrinology, doi:10.1210/en.2004-0645
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Endocrinology Vol. 146, No. 6 2709-2715
Copyright © 2005 by The Endocrine Society

Developmental Changes in the Pattern of Ghrelin’s Acyl Modification and the Levels of Acyl-Modified Ghrelins in Murine Stomach

Yoshihiro Nishi, Hiroshi Hiejima, Hiroharu Mifune, Takahiro Sato, Kenji Kangawa and Masayasu Kojima

Molecular Genetics, Institute of Life Science (Y.N., H.H., T.S., M.K.), and Institute of Animal Experimentation (H.M.), Kurume University, Fukuoka 839-0861; and Department of Biochemistry, National Cardiovascular Center Research Institute (K.K.), Osaka 565-8565, Japan

Address all correspondence and requests for reprints to: Dr. Masayasu Kojima, Molecular Genetics, Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0861, Japan. E-mail: mkojima{at}lsi.kurume-u.ac.jp.

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 Ser3 (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 Ser3 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.




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