Document Detail

Obesity in mice with adipocyte-specific deletion of clock component Arntl.
MedLine Citation:
PMID:  23142819     Owner:  NLM     Status:  MEDLINE    
Adipocytes store excess energy in the form of triglycerides and signal the levels of stored energy to the brain. Here we show that adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component, results in obesity in mice with a shift in the diurnal rhythm of food intake, a result that is not seen when the gene is disrupted in hepatocytes or pancreatic islets. Changes in the expression of hypothalamic neuropeptides that regulate appetite are consistent with feedback from the adipocyte to the central nervous system to time feeding behavior. Ablation of the adipocyte clock is associated with a reduced number of polyunsaturated fatty acids in adipocyte triglycerides. This difference between mutant and wild-type mice is reflected in the circulating concentrations of polyunsaturated fatty acids and nonesterified polyunsaturated fatty acids in hypothalamic neurons that regulate food intake. Thus, this study reveals a role for the adipocyte clock in the temporal organization of energy regulation, highlights timing as a modulator of the adipocyte-hypothalamic axis and shows the impact of timing of food intake on body weight.
Georgios K Paschos; Salam Ibrahim; Wen-Liang Song; Takeshige Kunieda; Gregory Grant; Teresa M Reyes; Christopher A Bradfield; Cheryl H Vaughan; Michael Eiden; Mojgan Masoodi; Julian L Griffin; Fenfen Wang; John A Lawson; Garret A Fitzgerald
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-11
Journal Detail:
Title:  Nature medicine     Volume:  18     ISSN:  1546-170X     ISO Abbreviation:  Nat. Med.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-11     Completed Date:  2013-02-11     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1768-77     Citation Subset:  IM    
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MeSH Terms
ARNTL Transcription Factors / deficiency*,  genetics
Absorptiometry, Photon
Adipocytes / metabolism*
Appetite Regulation / genetics*,  physiology
Blotting, Western
Chromatin Immunoprecipitation
Chromatography, Liquid
Circadian Rhythm / physiology*
DNA Primers / genetics
Discriminant Analysis
Energy Metabolism / genetics,  physiology*
Fatty Acids, Unsaturated / metabolism
Gene Deletion
Histological Techniques
Hypothalamus / metabolism
Mass Spectrometry
Neuropeptides / metabolism
Obesity / genetics*
Protein Array Analysis
Real-Time Polymerase Chain Reaction
Statistics, Nonparametric
Grant Support
BB/H013539/1//Biotechnology and Biological Sciences Research Council; MC_UP_A090_1006//Medical Research Council; P30 DK019525/DK/NIDDK NIH HHS; P30 DK19525/DK/NIDDK NIH HHS; R01 DK045586/DK/NIDDK NIH HHS; R01 DK45586/DK/NIDDK NIH HHS; R01 HL097800/HL/NHLBI NIH HHS; R01 HL097800/HL/NHLBI NIH HHS; UD99999906//Medical Research Council
Reg. No./Substance:
0/ARNTL Transcription Factors; 0/Arntl protein, mouse; 0/DNA Primers; 0/Fatty Acids, Unsaturated; 0/Neuropeptides
Comment In:
Nat Med. 2012 Dec;18(12):1738-40   [PMID:  23223058 ]

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

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