Document Detail


Fenofibrate simultaneously induces hepatic fatty acid oxidation, synthesis, and elongation in mice.
MedLine Citation:
PMID:  19801551     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A growing body of evidence indicates that peroxisome proliferator-activated receptor alpha (PPARalpha) not merely serves as a transcriptional regulator of fatty acid catabolism but also exerts a much broader role in hepatic lipid metabolism. We determined adaptations in hepatic lipid metabolism and related aspects of carbohydrate metabolism upon treatment of C57Bl/6 mice with the PPARalpha agonist fenofibrate. Stable isotope procedures were applied to assess hepatic fatty acid synthesis, fatty acid elongation, and carbohydrate metabolism. Fenofibrate treatment strongly induced hepatic de novo lipogenesis and chain elongation (+/-300, 150, and 600% for C16:0, C18:0, and C18:1 synthesis, respectively) in parallel with an increased expression of lipogenic genes. The lipogenic induction in fenofibrate-treated mice was found to depend on sterol regulatory element-binding protein 1c (SREBP-1c) but not carbohydrate response element-binding protein (ChREBP). Fenofibrate treatment resulted in a reduced contribution of glycolysis to acetyl-CoA production, whereas the cycling of glucose 6-phosphate through the pentose phosphate pathway presumably was enhanced. Altogether, our data indicate that beta-oxidation and lipogenesis are induced simultaneously upon fenofibrate treatment. These observations may reflect a physiological mechanism by which PPARalpha and SREBP-1c collectively ensure proper handling of fatty acids to protect the liver against cytotoxic damage.
Authors:
Maaike H Oosterveer; Aldo Grefhorst; Theo H van Dijk; Rick Havinga; Bart Staels; Folkert Kuipers; Albert K Groen; Dirk-Jan Reijngoud
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-30     Completed Date:  2009-12-22     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34036-44     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The Netherlands. M.H.Oosterveer@med.umcg.nl
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MeSH Terms
Descriptor/Qualifier:
Animals
Fatty Acids / metabolism*
Female
Fenofibrate / pharmacology*
Glucose-6-Phosphate / metabolism
Hypolipidemic Agents / pharmacology*
Lipid Metabolism
Liver / metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nuclear Proteins / metabolism
Oxygen / chemistry,  metabolism*
PPAR alpha / metabolism
Sterol Regulatory Element Binding Protein 1 / metabolism
Transcription Factors / metabolism
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Hypolipidemic Agents; 0/Nuclear Proteins; 0/PPAR alpha; 0/Sterol Regulatory Element Binding Protein 1; 0/Transcription Factors; 0/carbohydrate response element binding protein, mouse; 49562-28-9/Fenofibrate; 56-73-5/Glucose-6-Phosphate; 7782-44-7/Oxygen
Comments/Corrections

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


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