The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism.

Details

Serval ID
serval:BIB_6B964CD565A9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism.
Journal
FASEB Journal
Author(s)
Kersten S., Mandard S., Escher P., Gonzalez F.J., Tafuri S., Desvergne B., Wahli W.
ISSN
0892-6638[print], 0892-6638[linking]
Publication state
Published
Issued date
2001
Volume
15
Number
11
Pages
1971-1978
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
The peroxisome proliferator-activated receptor alpha is a ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. PPARalpha mediates the effects of fibrates, which are potent hypolipidemic drugs, on gene expression. To better understand the biological effects of fibrates and PPARalpha, we searched for genes regulated by PPARalpha using oligonucleotide microarray and subtractive hybridization. By comparing liver RNA from wild-type and PPARalpha null mice, it was found that PPARalpha decreases the mRNA expression of enzymes involved in the metabolism of amino acids. Further analysis by Northern blot revealed that PPARalpha influences the expression of several genes involved in trans- and deamination of amino acids, and urea synthesis. Direct activation of PPARalpha using the synthetic PPARalpha ligand WY14643 decreased mRNA levels of these genes, suggesting that PPARalpha is directly implicated in the regulation of their expression. Consistent with these data, plasma urea concentrations are modulated by PPARalpha in vivo. It is concluded that in addition to oxidation of fatty acids, PPARalpha also regulates metabolism of amino acids in liver, indicating that PPARalpha is a key controller of intermediary metabolism during fasting.
Keywords
Amino Acids/metabolism, Animals, Deamination, Gene Expression Regulation, Mice, Mice, Knockout, Nucleic Acid Hybridization/methods, Oligonucleotide Array Sequence Analysis/methods, Receptors, Cytoplasmic and Nuclear/genetics, Receptors, Cytoplasmic and Nuclear/physiology, Transcription Factors/genetics, Transcription Factors/physiology, Urea/metabolism
Pubmed
Web of science
Create date
24/01/2008 16:26
Last modification date
20/08/2019 15:25
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