Abstract

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.

Highlights

  • Ghrelin is a 28-amino acid peptide hormone, which was identified by Kojima and colleagues in 19991

  • The aim of this study was to determine the source of medium-chain fatty acids (MCFAs) that modify ghrelin; we examined the effect of diet, intestinal bacteria removal, and de novo synthesis or utilization of long chain fatty acids (LCFAs) in ghrelin-producing cells on acyl-ghrelin production in mice

  • The third serine of the ghrelin peptide is modified by MCFAs and this acyl-modification is pivotal for the physiological functions of ghrelin

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Summary

Introduction

Ghrelin is a 28-amino acid peptide hormone, which was identified by Kojima and colleagues in 19991 This hormone is mainly released from the stomach and has many physiological activities such as stimulating food intake[2], promoting growth hormone release[3], modulating gastrointestinal motility[4,5], decreasing blood pressure, and regulating energy metabolism[6]. We previously found that the oral administration of octanoic acid to hatched chicks increased the amount of acyl-ghrelin in the stomach[22] These results suggested that dietary MCFAs were directly used for ghrelin modification. The aim of this study was to determine the source of MCFAs that modify ghrelin; we examined the effect of diet, intestinal bacteria removal, and de novo synthesis or utilization of LCFAs in ghrelin-producing cells on acyl-ghrelin production in mice

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