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PPARα/HNF4α interplay on diversified responsive elements. Relevance in the regulation of liver peroxisomal fatty acid catabolism.
MedLine Citation:
PMID:  22978398     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In mammals, the liver is the major organ of fatty acid catabolism. This pathway is involved in both mitochondria and peroxisome. While mitochondria breaks down fatty acids with short, medium and long carbon chains, peroxisomes are involved in the catabolism of very long and branched chain fatty acids, which are degraded by three enzymes: acyl-CoA oxidase, multifunctional enzyme and thiolase enzyme. The active pathway results mainly from a tight transcriptional control of these gene-encoding enzymes. Two major nuclear receptors that are highly expressed in this organ are involved in this control, e.g. PPAR α (peroxisome proliferator-activated receptor, α isoform) and HNF4α (hepatic nuclear factor 4, α isotype). Both are key regulators of liver lipid metabolism. While numerous papers have reported on the role of PPARα in liver lipid homeostasis, less is known on the implication of HNF4α in this metabolism. Moreover, very few studies have taken an interest in the important question of the implication of these two receptors and most particularly their crosstalk. This review therefore presents the current knowledge on the PPAR α /HNF4 α interplay in diversified DNA responsive elements and its relevance in the regulation fatty acid catabolism. It presents a review of the properties of the nuclear receptors PPAR α and HNF4 α, then the genes regulated by HNF4 α and PPAR α, particularly the peroxisomal enzyme target genes. To conclude, the consequences of the regulation of these genes in the liver by PPAR α and HNF4 α will be analyzed. The current data indicate the requirement of PPAR α and HNF4 α for regulation in the liver of peroxisomal and mitochondrial fatty acid α -oxidation, cholesterol and bile acid metabolism, lipoprotein metabolism and consequently the prevention of liver steatosis. However, several questions remain unsolved. To show the interplay of PPAR α and HNF4 α in the regulation of liver fatty acid metabolism, different strategies are proposed.
Authors:
Julie Chamouton; Norbert Latruffe
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-04
Journal Detail:
Title:  Current drug metabolism     Volume:  -     ISSN:  1875-5453     ISO Abbreviation:  Curr. Drug Metab.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100960533     Medline TA:  Curr Drug Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Inserm U866, Dijon, F-21000, France. norbert.latruffe@u-bourgogne.fr.
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