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Endogenous ghrelin‐O‐acyltransferase ( GOAT ) acylates local ghrelin in the hippocampus
Author(s) -
Murtuza Mohammad I.,
Isokawa Masako
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14244
Subject(s) - ghrelin , growth hormone secretagogue receptor , medicine , endocrinology , biology , receptor , hippocampal formation , hippocampus , endogeny , hypothalamus , dentate gyrus , hormone
Abstract Ghrelin is an appetite‐stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin‐O‐acyltransferase ( GOAT ) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a ( GHSR 1a). Interest in GHSR 1a increased dramatically when GHSR 1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR 1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non‐octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild‐type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR 1a or the metabolic state‐dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR 1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR 1a may be a prerequisite for the production of GOAT . Application of fluorescein isothiocyanate ( FITC )‐conjugated non‐octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC ‐conjugated octanoylated ghrelin, suggesting that extracellularly applied non‐octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain.