Differential roles for cholecystokinin a receptors in energy balance in rats and mice.
Although cholecystokinin A (CCK-A) receptors (CCK-AR) mediate the feeding inhibitory actions of CCK in both rats and mice, the absence of CCK-AR results in species-specific phenotypes. The lack of CCK-AR in Otsuka Long-Evans Tokushima fatty (OLETF) rats results in hyperphagia and obesity. We have suggested that demonstrated increases in meal size and elevated levels of dorsomedial hypothalamic (DMH) neuropeptide Y (NPY) gene expression may contribute to this phenotype. In contrast to OLETF rats, CCK-AR(-/-) mice have normal total daily food intake and do not develop obesity. To assess the basis underlying the different phenotypes in rats and mice lacking CCK-AR, we characterized meal patterns in CCK-AR(-/-) mice and determined whether CCK-AR(-/-) mice exhibited an alteration in DMH NPY gene expression. We demonstrate that although CCK-AR(-/-) mice show a similar dysregulation in meal size as OLETF rats, they do not have an elevation in DMH NPY mRNA expression levels. In fact, intact mice have no CCK-AR in the DMH. Furthermore, in intact rats, NPY and CCK-AR are colocalized in DMH neurons, and parenchymal injection of CCK into the DMH reduces food intake and down-regulates DMH NPY mRNA expression. These results suggest that although CCK-AR plays a role in the mediation of CCK actions in the control of meal size in both rats and mice, CCK-AR seems to contribute to modulating DMH NPY levels only in rats. The deficit in CCK's action in the control of DMH NPY gene expression may play a major role in the obese phenotype in OLETF rats.
Bi
Sheng
S
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. sbi@jhmi.edu.
Scott
Karen A
KA
Kopin
Alan S
AS
Moran
Timothy H
TH
D000818:Animals; D004734:Energy Metabolism; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D043886:Receptor, Cholecystokinin A / Q000502:physiology*
D009478:Neuropeptide Y; D012333:RNA, Messenger; D043886:Receptor, Cholecystokinin A