Effect of peripheral obestatin on food intake and gastric emptying in ghrelin-knockout mice.
OBJECTIVE
The finding that obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's stimulatory effect on food intake and gastric emptying has been questioned. The effect of obestatin has been mostly investigated in fasted rodents, a condition associated with high blood levels of ghrelin which may mask the effect of obestatin. We therefore investigated the effect of obestatin on food intake, gastric emptying and gastric contractility in ghrelin knockout mice.


METHODS
The effect of obestatin on 6-h cumulative food intake was studied in fasted wildtype (ghrelin+/+) and ghrelin knockout (ghrelin-/-) mice. In both genotypes, the effect of obestatin and/or ghrelin was studied in vivo on gastric emptying measured with the (14)C-octanoic acid breath test and in vitro on neural responses elicited by electrical field stimulation (EFS) of fundic smooth muscle strips.


RESULTS
Administration of obestatin did not influence fasting-induced hyperphagia or gastric emptying in both genotypes. Injection of ghrelin accelerated gastric emptying in ghrelin+/+ and ghrelin-/- mice but the effect was not reversed by co-injection with obestatin. In fundic strips from ghrelin+/+ and ghrelin-/- mice, ghrelin increased EFS-induced contractions, but obestatin was without effect. However, co-administration with obestatin tended to reduce the excitatory effect of ghrelin in both genotypes.


CONCLUSIONS
In ghrelin-/- mice, obestatin failed to affect food intake and gastric motility. These results suggest that endogenous ghrelin does not mask the effect of obestatin and confirm that obestatin administered peripherally is not a major regulator of satiety signalling or gut motility.
Depoortere
I
I
Centre for Gastroenterological Research, Catholic University of Leuven, Leuven, Belgium. inge.depoortere@med.kuleuven.be
Thijs
T
T
Moechars
D
D
De Smet
B
B
Ver Donck
L
L
Peeters
T L
TL
D000818:Animals; D001944:Breath Tests; D002210:Caprylates; D018592:Cross-Over Studies; D004435:Eating / Q000187:drug effects*; D004558:Electric Stimulation; D005746:Gastric Emptying / Q000187:drug effects*; D005748:Gastric Fundus / Q000187:drug effects / Q000378:metabolism; D005838:Genotype; D054439:Ghrelin / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D002210:Caprylates; D054439:Ghrelin