Forskning ved Københavns Universitet - Københavns Universitet

Forside

Acylation type determines ghrelin's effects on energy homeostasis in rodents

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Kristy Heppner
  • Nilika Chaudhary
  • Timo D Müller
  • Henriette Kirchner
  • Kirk M Habegger
  • Nickki Ottaway
  • David L Smiley
  • Richard Dimarchi
  • Susanna M Hofmann
  • Stephen C Woods
  • Bjørn Behrens Sivertsen
  • Holst, Birgitte
  • Paul T Pfluger
  • Diego Perez-Tilve
  • Matthias H Tschöp
Ghrelin is a gastrointestinal polypeptide that acts through the ghrelin receptor (GHSR) to promote food intake and increase adiposity. Activation of GHSR requires the presence of a fatty-acid (FA) side chain on amino acid residue serine 3 of the ghrelin molecule. However, little is known about the role that the type of FA used for acylation plays in the biological action of ghrelin. We therefore evaluated a series of differentially acylated peptides to determine whether alterations in length or stability of the FA side chain have an impact on the ability of ghrelin to activate GHSR in vitro or to differentially alter food intake, body weight, and body composition in vivo. Fatty acids principally available in the diet (such as palmitate C16) and therefore representing potential substrates for the ghrelin-activating enzyme ghrelin O-acyltransferase (GOAT) were used for dose-, time-, and administration/route-dependent effects of ghrelin on food intake, body weight, and body composition in rats and mice. Our data demonstrate that altering the length of the FA side chain of ghrelin results in the differential activation of GHSR. Additionally, we found that acylation of ghrelin with a long-chain FA (C16) delays the acute central stimulation of food intake. Lastly, we found that, depending on acylation length, systemic and central chronic actions of ghrelin on adiposity can be enhanced or reduced. Together our data suggest that modification of the FA side-chain length can be a novel approach to modulate the efficacy of pharmacologically administered ghrelin.
OriginalsprogEngelsk
BogserieContemporary Endocrinology
Vol/bind153
Udgave nummer10
Sider (fra-til)4687-95
Antal sider9
ISSN0196-8653
DOI
StatusUdgivet - okt. 2012

ID: 46279971