Fasting induces CART down-regulation in the zebrafish nervous system in a cannabinoid receptor 1-dependent manner.
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.
Institut de Genomique Fonctionelle de Lyon, Unité Mixte de Recherche 5242 du Centre National de la Recherche Scientifique, Université de Lyon, Lyon, France.
Shin-Ichi
S
Nishio
Yann
Y
Gibert
Liubov
L
Berekelya
Laure
L
Bernard
Frédéric
F
Brunet
Etienne
E
Guillot
Jean-Christophe
JC
Le Bail
Juan Antonio
JA
Sánchez
Anne Marie
AM
Galzin
Gerard
G
Triqueneaux
Vincent
V
Laudet
D000818:Animals; D001069:Appetite Regulation; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D015536:Down-Regulation; D005508:Food Deprivation; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D007814:Larva / Q000378:metabolism; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism; D000077285:Rimonabant; D015017:Yolk Sac / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
D063386:Cannabinoid Receptor Agonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D000077285:Rimonabant