Back to Search Start Over

Fasting induces CART down-regulation in the zebrafish nervous system in a cannabinoid receptor 1-dependent manner.

Authors :
Nishio S
Gibert Y
Berekelya L
Bernard L
Brunet F
Guillot E
Le Bail JC
Sánchez JA
Galzin AM
Triqueneaux G
Laudet V
Source :
Molecular endocrinology (Baltimore, Md.) [Mol Endocrinol] 2012 Aug; Vol. 26 (8), pp. 1316-26. Date of Electronic Publication: 2012 Jun 14.
Publication Year :
2012

Abstract

Central and peripheral mechanisms modulate food intake and energy balance in mammals and the precise role of the type 1 cannabinoid receptor (CB1) in these processes is still being explored. Using the zebrafish, Danio rerio, we show that rimonabant, a CB1-specific antagonist with an EC(50) of 5.15 × 10(-8) m, decreases embryonic yolk sac reserve use. We reveal a developmental overlap between CART genes and CB1 expression in the hypothalamus and medulla oblongata, two brain structures that play crucial roles in appetite regulation in mammals. We show that morpholino knockdown of CB1 or fasting decreases cocaine- and amphetamine-related transcript (CART)-3 expression. Strikingly, this down-regulation occurs only in regions coexpressing CB1 and CART3, reinforcing the link between CB1, CART, and appetite regulation. We show that rimonabant treatment impairs the fasting-induced down-regulation of CART expression in specific brain regions, whereas vehicle alone-treated embryos do not display this rescue of CART expression. Our data reveal that CB1 lies upstream of CART and signals the appetite through the down-regulation of CART expression. Thus, our results establish the zebrafish as a promising system to study appetite regulation.

Details

Language :
English
ISSN :
1944-9917
Volume :
26
Issue :
8
Database :
MEDLINE
Journal :
Molecular endocrinology (Baltimore, Md.)
Publication Type :
Academic Journal
Accession number :
22700585
Full Text :
https://doi.org/10.1210/me.2011-1180