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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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