|Obesity in mice with adipocyte-specific deletion of clock component Arntl.|
|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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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-11-11|
|Title: Nature medicine Volume: 18 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2012 Dec|
|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|
|Languages: eng Pagination: 1768-77 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
ARNTL Transcription Factors
Adipocytes / metabolism*
Appetite Regulation / genetics*, physiology
Circadian Rhythm / physiology*
DNA Primers / genetics
Energy Metabolism / genetics, physiology*
Fatty Acids, Unsaturated / metabolism
Hypothalamus / metabolism
Neuropeptides / metabolism
Obesity / genetics*
Protein Array Analysis
Real-Time Polymerase Chain Reaction
|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|
|0/ARNTL Transcription Factors; 0/Arntl protein, mouse; 0/DNA Primers; 0/Fatty Acids, Unsaturated; 0/Neuropeptides|
|Nat Med. 2012 Dec;18(12):1738-40
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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