Document Detail


Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene.
MedLine Citation:
PMID:  23115121     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CCK is hypothesized to inhibit meal size by acting at CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. Earlier studies have shown that obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic and obese. Recent findings show that rats with CCK1R-null gene on a Fischer 344 background (Cck1r(-/-)) are lean and normophagic. In this study, the metabolic phenotype of this rat strain was further characterized. As expected, the CCK1R antagonist, devazepide, failed to stimulate food intake in the Cck1r(-/-) rats. Both Cck1r(+/+) and Cck1r(-/-) rats became diet-induced obese (DIO) when maintained on a high-fat diet relative to chow-fed controls. Cck1r(-/-) rats consumed larger meals than controls during the dark cycle and smaller meals during the light cycle. These effects were accompanied by increased food intake, total spontaneous activity, and energy expenditure during the dark cycle and an apparent reduction in respiratory quotient during the light cycle. To assess whether enhanced responsiveness to anorexigenic factors may contribute to the lean phenotype, we examined the effects of melanotan II (MTII) on food intake and body weight. We found an enhanced effect of MTII in Cck1r(-/-) rats to suppress food intake and body weight following both central and peripheral administration. These results suggest that the lean phenotype is potentially driven by increases in total spontaneous activity and energy expenditure.
Authors:
James E Blevins; Daniel H Moralejo; Tami H Wolden-Hanson; Brendan S Thatcher; Jacqueline M Ho; Karl J Kaiyala; Kozo Matsumoto
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-10-31
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  303     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-02-21     Revised Date:  2013-12-18    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1231-40     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects,  physiology
Devazepide / pharmacology
Eating / drug effects,  physiology
Energy Metabolism / physiology*
Gene Deletion
Male
Models, Animal
Motor Activity / physiology*
Peptides, Cyclic / pharmacology
Phenotype*
Rats
Rats, Inbred F344
Rats, Mutant Strains
Receptor, Cholecystokinin A / antagonists & inhibitors,  deficiency*,  genetics
Sequence Deletion / genetics
Thinness / physiopathology*
alpha-MSH / analogs & derivatives,  pharmacology
Grant Support
ID/Acronym/Agency:
DK-17047/DK/NIDDK NIH HHS; P30DK017047-31/DK/NIDDK NIH HHS; P30KD017047-31689//PHS HHS; R01DK-61516/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Peptides, Cyclic; 0/Receptor, Cholecystokinin A; 121062-08-6/melanotan-II; 581-05-5/alpha-MSH; JE6P7QY7NH/Devazepide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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