IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
artículos
Título:
GOAT induced ghrelin acylation regulates hedonic feeding
Autor/es:
DAVIS, JF; PERELLO, M; CHOI, DL; MAGRISSO, IJ; KIRCHNER, H; PFLUGER, PT; TSCHOP, M; ZIGMAN, JM; BENOIT, SC
Revista:
HORMONES AND BEHAVIOR
Editorial:
ACADEMIC PRESS INC ELSEVIER SCIENCE
Referencias:
Lugar: Amsterdam; Año: 2012 p. 598 - 604
ISSN:
0018-506X
Resumen:
Ghrelin is an orexigenic hormone that regulates homeostatic and
reward-related feeding behavior. Recent evidence indicates that acylation of
ghrelin by the gut enzyme ghrelin O-acyl transferase (GOAT) is necessary to
render ghrelin maximally active within its target tissues. Here we tested the
hypothesis that GOAT activity modulates food motivation and food hedonics using
behavioral pharmacology and mutant mice deficient for GOAT and the ghrelin
receptor (GHSR). We evaluated operant responding following pharmacological
administration of acyl-ghrelin and assessed the necessity of endogenous GOAT
activity for operant responding in GOAT and GHSR-null mice. Hedonic-based
feeding behavior also was examined in GOAT-KO and GHSR-null mice using a
"Dessert Effect" protocol in which the intake of a palatable high fat
diet "dessert" was assessed in calorically-sated mice.
Pharmacological administration of acyl-ghrelin augmented operant responding;
notably, this effect was dependent on intact GHSR signaling. GOAT-KO mice
displayed attenuated operant responding and decreased hedonic feeding relative
to controls. These behavioral results correlated with decreased expression of
the orexin-1 receptor in reward-related brain regions in GOAT-KO mice. In
summary, the ability of ghrelin to stimulate food motivation is dependent on
intact GHSR signaling and modified by endogenous GOAT activity. Furthermore,
GOAT activity is required for hedonic feeding behavior, an effect potentially
mediated by forebrain orexin signaling. These data highlight the significance
of the GOAT-ghrelin system for the mediation of food motivation and hedonic
feeding.