Document Detail

Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle.
MedLine Citation:
PMID:  19837866     Owner:  NLM     Status:  MEDLINE    
Melanocortin-3 receptors (Mc3rs) in the central nervous system are involved in expression of anticipatory rhythms and synchronizing clocks maintaining circadian rhythms during restricted feeding (RF) [mice housed under a 12-h light-dark cycle with lights on between zeitgeber time (ZT) 0 to ZT12 fed 60% of normal calories between ZT7 and ZT11]. Because the systems governing circadian rhythms are important for adaptation to RF, we investigated whether Mc3rs are required for metabolic adaption to RF. Mc3r(-/-) mice subjected to RF exhibited normal weight loss; however, they developed hyperinsulinemia, glucose intolerance, increased expression of lipogenic genes, and increased ketogenesis relative to controls. Rhythmic expression of transcription factors regulating liver clock activity and energy metabolism (Bmal1, Rev-erbalpha, Pgc1, Foxo1, Hnf4alpha, and Pck1) was severely compromised in Mc3r(-/-) mice during RF. Inhibition of neural melanocortin receptors by agouti-related peptide also attenuated rhythmicity in the hepatic expression of these genes during RF. Collectively, these data suggest that neural Mc3rs are important for adapting metabolism and maintaining rhythms of liver metabolism during periods when feeding is restricted to the light cycle.-Sutton, G. M., Begriche, K., Kumar, K. G., Gimble, J. M., Perez-Tilve, D., Nogueiras, R., McMillan, R. P., Hulver, M. W., Tschöp, M. H., Butler, A. A. Central nervous system melanocortin-3 receptors are required for synchronizing metabolism during entrainment to restricted feeding during the light cycle.
Gregory M Sutton; Karima Begriche; K Ganesh Kumar; Jeffrey M Gimble; Diego Perez-Tilve; Ruben Nogueiras; Ryan P McMillan; Matthew W Hulver; Matthias H Tschöp; Andrew A Butler
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-10-16
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  24     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-05-11     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  862-72     Citation Subset:  IM    
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MeSH Terms
Agouti-Related Protein / pharmacology
Caloric Restriction*
Central Nervous System / metabolism*,  radiation effects
Electrophoresis, Polyacrylamide Gel
Energy Metabolism / drug effects,  genetics
Fatty Acids / metabolism
Forkhead Transcription Factors / metabolism
Glucose Intolerance / genetics
Glucose Tolerance Test
Hyperinsulinism / genetics
Liver / drug effects,  metabolism
Mice, Mutant Strains
Receptor, Melanocortin, Type 3 / antagonists & inhibitors,  genetics,  physiology*
Grant Support
Reg. No./Substance:
0/Agouti-Related Protein; 0/Fatty Acids; 0/Forkhead Transcription Factors; 0/Foxo1 protein, mouse; 0/Receptor, Melanocortin, Type 3

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