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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6963
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pubmed:dateCreated |
2003-11-17
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pubmed:abstractText |
Fasting triggers a series of hormonal cues that promote energy balance by inducing glucose output and lipid breakdown in the liver. In response to pancreatic glucagon and adrenal cortisol, the cAMP-responsive transcription factor CREB activates gluconeogenic and fatty acid oxidation programmes by stimulating expression of the nuclear hormone receptor coactivator PGC-1 (refs 2-5). In parallel, fasting also suppresses lipid storage and synthesis (lipogenic) pathways, but the underlying mechanism is unknown. Here we show that mice deficient in CREB activity have a fatty liver phenotype and display elevated expression of the nuclear hormone receptor PPAR-gamma, a key regulator of lipogenic genes. CREB inhibits hepatic PPAR-gamma expression in the fasted state by stimulating the expression of the Hairy Enhancer of Split (HES-1) gene, a transcriptional repressor that is shown here to be a mediator of fasting lipid metabolism in vivo. The coordinate induction of PGC-1 and repression of PPAR-gamma by CREB during fasting provides a molecular rationale for the antagonism between insulin and counter-regulatory hormones, and indicates a potential role for CREB antagonists as therapeutic agents in enhancing insulin sensitivity in the liver.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/HES1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hes1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Triglycerides
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1476-4687
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
13
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pubmed:volume |
426
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
190-3
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:14614508-Animals,
pubmed-meshheading:14614508-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:14614508-Cell Line, Tumor,
pubmed-meshheading:14614508-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:14614508-Fasting,
pubmed-meshheading:14614508-Fatty Liver,
pubmed-meshheading:14614508-Gene Expression Regulation,
pubmed-meshheading:14614508-Homeodomain Proteins,
pubmed-meshheading:14614508-Humans,
pubmed-meshheading:14614508-Insulin,
pubmed-meshheading:14614508-Lipid Metabolism,
pubmed-meshheading:14614508-Liver,
pubmed-meshheading:14614508-Male,
pubmed-meshheading:14614508-Mice,
pubmed-meshheading:14614508-Mice, Inbred C57BL,
pubmed-meshheading:14614508-Phenotype,
pubmed-meshheading:14614508-Receptors, Cytoplasmic and Nuclear,
pubmed-meshheading:14614508-Transcription Factors,
pubmed-meshheading:14614508-Triglycerides
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pubmed:year |
2003
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pubmed:articleTitle |
CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma.
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pubmed:affiliation |
Peptide Biology Laboratories Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037-1002, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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