Dridi S, Ververken C, Hillgartner FB, Lutgarde
A, Van der Gucht E, Cnops L, Decuypere E, Buyse J.
CERULENIN : FAS
inhibitor cerulenin reduces food intake and melanocortin
receptor gene expression without modulating the other (an)orexigenic
neuropeptides in chickens.
Am J Physiol Regul Integr Comp Physiol. 2006
Jul;291(1):R138-47
Laboratory of Physiology and Immunology of Domestic Animals,
Catholic University of Leuven, Heverlee, Belgium.
Sami.Dridi@agr.kuleuven.ac.be
Cerulenin, a natural fatty acid synthase (FAS) inhibitor, and
its synthetic analog C75 are hypothesized to alter the
metabolism of neurons in the hypothalamus that regulate
ingestive behavior to cause a profound decrease of food intake
and an increase in metabolic rate, leading to body weight loss.
The bulk of data exclusively originates from mammals (rodents);
however, such effects are currently lacking in nonmammalian
species. We have, therefore, addressed this issue in broiler
chickens because this species is selected for high growth rate
and high food intake and is prone to obesity. First, we
demonstrate that FAS messenger and protein are expressed in the
hypothalamus of chickens. FAS immunoreactivity was detected in a
number of brain regions, including the nucleus paraventricularis
magnocellularis and the nucleus infundibuli hypothalami, the
avian equivalent of the mammalian arcuate nucleus, suggesting
that FAS may be involved in the regulation of food intake.
Second, we show that hypothalamic FAS gene expression was
significantly (P < 0.05) decreased by overnight fasting similar
to that in liver, indicating that hypothalamic FAS gene is
regulated by energy status in chickens. Finally, to investigate
the physiological consequences of in vivo inhibition of fatty
acid synthesis on food intake, we administered cerulenin by
intravenous injections (15 mg/kg) to 2-wk-old broiler chickens.
Cerulenin administration significantly reduced food intake by 23
to 34% (P < 0.05 to P < 0.0001) and downregulated FAS and
melanocortin receptors 1, 4, and 5 gene expression (P < 0.05).
However, the known orexigenic (neuropeptide Y, agouti
gene-related peptide, orexin, and orexin receptor) and
anorexigenic (pro-opiomelanocortin and corticotropin-releasing
hormone) neuropeptide mRNA levels remained unchanged after
cerulenin treatment. These results suggest that the catabolic
effect of cerulenin in chickens may be mediated through the
melanocortin system rather than the other neuropeptides known to
be involved in food intake regulation.
PMID: 16455759 |
