AUTHOR=Nishi Yoshihiro , Mifune Hiroharu , Yabuki Akira , Tajiri Yuji , Hirata Rumiko , Tanaka Eiichiro , Hosoda Hiroshi , Kangawa Kenji , Kojima Masayasu 

TITLE=Changes in Subcellular Distribution of n-Octanoyl or n-Decanoyl Ghrelin in Ghrelin-Producing Cells

JOURNAL=Frontiers in Endocrinology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2013.00084

DOI=10.3389/fendo.2013.00084

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> The enzyme ghrelin <italic>O</italic>-acyltransferase (GOAT) catalyzes the acylation of ghrelin. The molecular form of GOAT, together with its reaction <italic>in vitro</italic>, has been reported previously. However, the subcellular processes governing the acylation of ghrelin remain to be elucidated.</p><p><bold>Methods:</bold> Double immunoelectron microscopy was used to examine changes in the relative proportions of secretory granules containing <italic>n</italic>-octanoyl ghrelin (C8-ghrelin) or <italic>n</italic>-decanoyl ghrelin (C10-ghrelin) in ghrelin-producing cells of mouse stomachs. The dynamics of C8-type (possessing C8-ghrelin exclusively), C10-type (possessing C10-ghrelin only), and mixed-type secretory granules (possessing both C8- and C10-ghrelin) were investigated after fasting for 48 h or after 2 weeks feeding with chow containing glyceryl-tri-octanoate (C8-MCT) or glyceryl-tri-decanoate (C10-MCT). The dynamics of C8- or C10-ghrelin-immunoreactivity (ir-C8- or ir-C10-ghrelin) within the mixed-type granules were also investigated.</p><p><bold>Results:</bold> Immunoelectron microscopic analysis revealed the co-existence of C8- and C10-ghrelin within the same secretory granules (mixed-type) in ghrelin-producing cells. Compared to control mice fed standard chow, the ratio of C10-type secretory granules increased significantly after ingestion of C10-MCT, whereas that of C8-type granules declined significantly under the same treatment. After ingestion of C8-MCT, the proportion of C8-type secretory granules increased significantly. Within the mixed-type granules the ratio of ir-C10-ghrelin increased significantly and that of ir-C8-ghrelin decreased significantly upon fasting.</p><p><bold>Conclusion:</bold> These findings confirmed that C10-ghrelin, another acyl-form of active ghrelin, is stored within the same secretory granules as C8-ghrelin, and suggested that the types of medium-chain acyl-molecules surrounding and available to the ghrelin-GOAT system may affect the physiological processes of ghrelin acylation.</p>