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Department of Molecular Genetics (Y.N., H.Hi., Y.F., M.K.), Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0861; Department of Biochemistry (H.Ho., H.K., K.M., K.K), National Cardiovascular Center Research Institute, Osaka 565-8565; and Department of Bioregulatory Science (T.Y., H.N.), Graduate School of Medical Science, Kyushu University, Fukuoka 812-8582, Japan
Address all correspondence and requests for reprints to: Masayasu Kojima, M.D., Ph.D., Molecular Genetics, Institute of Life Science, Kurume University, Kurume-city, Fukuoka 839-0861, Japan. E-mail-1: mkojima{at}lsi.kurume-u.ac.jp; or nishi{at}lsi.kurume-u.ac.jp.
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.
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