Developmental changes in the pattern of ghrelin's acyl modification and the levels of acyl-modified ghrelins in murine stomach

Endocrinology. 2005 Jun;146(6):2709-15. doi: 10.1210/en.2004-0645. Epub 2005 Mar 3.

Abstract

Ghrelin is an acylated peptide hormone secreted primarily from endocrine cells in the stomach. The major active form of ghrelin is a 28-amino acid peptide with an n-octanoyl modification at Ser(3) (n-octanoyl ghrelin), which is essential for its activity. In addition to n-octanoyl ghrelin, other forms of ghrelin peptide exist, including des-acyl ghrelin, which lacks an acyl modification, and other minor acylated ghrelin species, such as n-decanoyl ghrelin, whose Ser(3) residue is modified by n-decanoic acid. Multiple reports have identified various physiological functions of ghrelin. However, until now, there have been no reports that explore the process of ghrelin acyl modification, and only a few studies have compared the levels of des-acyl, n-octanoyl, and/or other minor populations of acylated ghrelin peptides. In this study we report that the amount of n-octanoyl ghrelin in murine stomachs increases gradually during the suckling period to a maximal level at 3 wk of age and falls sharply after the initiation of weaning. However, the concentration (picomoles per milligram of wet weight tissue) of total ghrelin, which includes des-acyl and all acylated forms of ghrelin peptides with intact C termini in murine stomach, remains unchanged across this suckling-weaning transition. Prematurely weaned mice exhibited a significant decrease in the amount of n-octanoyl or n-decanoyl ghrelin in the stomach. Orally ingested glyceryl trioctanoate, a medium-chain triacylglyceride rich in milk lipids, significantly increased the level of n-octanoyl-modified ghrelin in murine stomach. Fluctuations in the proportion of this biologically active, acyl-modified ghrelin could contribute to or be influenced by the change in energy metabolism during the suckling-weaning transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Age Factors
  • Animals
  • Animals, Suckling
  • Dietary Fats / pharmacology
  • Energy Metabolism / physiology
  • Gastric Mucosa / metabolism*
  • Ghrelin
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Milk
  • Peptide Hormones / blood
  • Peptide Hormones / metabolism*
  • Rats
  • Rats, Wistar
  • Stomach / growth & development*
  • Triglycerides / metabolism
  • Weaning

Substances

  • Dietary Fats
  • Ghrelin
  • Peptide Hormones
  • Triglycerides
  • ghrelin, des-n-octanoyl