Differential roles for cholecystokinin A receptors in energy balance in rats and mice

Sheng Bi, Karen A. Scott, Alan S. Kopin, Timothy H. Moran

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3873-3880
Number of pages8
JournalEndocrinology
Volume145
Issue number8
DOIs
StatePublished - Aug 2004

ASJC Scopus subject areas

  • Endocrinology

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