Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source for ghrelin acyl-modification is not known. We found that a fat-free diet and the removal of intestinal microbiota did not decrease acyl-ghrelin production in the stomach or plasma acyl-ghrelin levels in mice. RT-PCR analysis showed that genes involving fatty acid synthesis, metabolism, and transport were expressed in pancreas-derived ghrelinoma (PG-1) cells. Treatment with an irreversible inhibitor of carnitine palmitoyltransferase-1 (CPT-1) strongly decreased acylated ghrelin levels but did not affect ghrelin or ghrelin o-acyl transferase (GOAT) mRNA levels in PG-1 cells. Our results suggest that the medium-chain fatty acid used for the acyl-modification of ghrelin is produced in ghrelin-producing cells themselves by β-oxidation of long-chain fatty acids provided from the circulation.
Ghrelin is abundantly produced in the stomach. Here, we found that glutamate decreased ghrelin expression and release in ghrelin-producing cells, and decreased levels of food intake and plasma acyl-ghrelin in mice. Treatment with siRNA of G protein-coupled receptor, family C, group 5, member B (GPRC5B) in ghrelin-producing cell lines completely blocked the effect of glutamate-induced ghrelin suppression. In addition, glutamate inhibited ghrelin release via the extracellular signal-regulated kinase (ERK) activity pathway, and stimulated CREB2 mRNA expression in ghrelin-producing cell lines. These results suggest that glutamate inhibits ghrelin release via ERK-CREB2 pathway. These results suggest that the GPRC5B-ERK-CREB2 pathway is involved in the inhibition of ghrelin expression and secretion in ghrelin cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.