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Heppner, K.M.* ; Chaudhary, N.* ; Müller, T.D. ; Kirchner, H.* ; Habegger, K.M.* ; Ottaway, N.* ; Smiley, D.L.* ; DiMarchi, R.* ; Hofmann, S.M. ; Woods, S.C.* ; Sivertsen, B.* ; Holst, B.* ; Pfluger, P.T.* ; Perez-Tilve, D.* ; Tschöp, M.H.

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

Endocrinology 153, 4687-4695 (2012)
Verlagsversion Volltext DOI PMC
Free by publisher
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter HORMONE SECRETAGOGUE RECEPTOR; CHAIN FATTY-ACIDS; PLASMA GHRELIN; FOOD-INTAKE; CIRCULATING GHRELIN; ARCUATE NUCLEUS; PEPTIDE-HORMONE; NEUROPEPTIDE-Y; BINDING-SITES; MESSENGER-RNA
ISSN (print) / ISBN 0013-7227
e-ISSN 1945-7170
Zeitschrift Endocrinology
Quellenangaben Band: 153, Heft: 10, Seiten: 4687-4695 Artikelnummer: , Supplement: ,
Verlag Endocrine Society
Verlagsort Chevy Chase, Md.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Institute of Experimental Genetics (IEG)