ZFIN ID: ZDB-PUB-120702-5
Fasting Induces CART Down-Regulation in the Zebrafish Nervous System in a Cannabinoid Receptor 1-Dependent Manner
Nishio, S.I., Gibert, Y., Berekelya, L., Bernard, L., Brunet, F., Guillot, E., Le Bail, J.C., Sánchez, J.A., Galzin, A.M., Triqueneaux, G., and Laudet, V.
Date: 2012
Source: Molecular endocrinology (Baltimore, Md.)   26(8): 1316-1326 (Journal)
Registered Authors: Brunet, Frederic G., Gibert, Yann, Laudet, Vincent, Triqueneaux, Gérard
Keywords: none
MeSH Terms:
  • Animals
  • Appetite Regulation*
  • Brain/embryology
  • Brain/metabolism*
  • Cannabinoid Receptor Agonists/pharmacology
  • Down-Regulation*
  • Food Deprivation*
  • Gene Expression Regulation, Developmental
  • Gene Knockdown Techniques
  • Larva/metabolism
  • Molecular Sequence Data
  • Obesity/metabolism
  • Obesity/physiopathology
  • Piperidines/pharmacology
  • Pyrazoles/pharmacology
  • Receptor, Cannabinoid, CB1/agonists
  • Receptor, Cannabinoid, CB1/genetics
  • Receptor, Cannabinoid, CB1/metabolism*
  • Receptor, Cannabinoid, CB2/genetics
  • Receptor, Cannabinoid, CB2/metabolism
  • Yolk Sac/metabolism
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish/physiology
PubMed: 22700585 Full text @ Mol. Endocrinol.

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 EC50 of 5.15 × 108 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.