β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification

Sci Rep. 2018 Jun 15;8(1):9176. doi: 10.1038/s41598-018-27458-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Acyltransferases / antagonists & inhibitors
  • Acyltransferases / metabolism
  • Animals
  • Carnitine O-Palmitoyltransferase / antagonists & inhibitors
  • Carnitine O-Palmitoyltransferase / metabolism
  • Cell Line, Tumor
  • Enzyme Inhibitors / pharmacology
  • Fatty Acids / metabolism*
  • Ghrelin / metabolism*
  • Male
  • Mice
  • Oxidation-Reduction
  • Protein Processing, Post-Translational*
  • RNA, Messenger / metabolism

Substances

  • Enzyme Inhibitors
  • Fatty Acids
  • Ghrelin
  • RNA, Messenger
  • Acyltransferases
  • Carnitine O-Palmitoyltransferase
  • ghrelin O-acyltransferase, rat