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regulates amino acid metabolism
Institut de Biologie Animale, Université de Lausanne, CH-1015, Lausanne, Switzerland;
* Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, Michigan 48105, USA; and
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
1Correspondence: Nutrition, Metabolism and Genomics Group, Wageningen University, P.O. Box 8129, 6700 EV Wageningen, The Netherlands. E-mail: sander.kersten{at}staff.nutepi.wau.nl
The peroxisome proliferator-activated receptor 
is a ligand-activated
transcription factor that plays an important role in the regulation of
lipid homeostasis. PPAR mediates the effects of fibrates, which are
potent hypolipidemic drugs, on gene expression. To better understand
the biological effects of fibrates and PPAR, we searched for genes
regulated by PPAR using oligonucleotide microarray and subtractive
hybridization. By comparing liver RNA from wild-type and PPAR null
mice, it was found that PPAR decreases the mRNA expression of
enzymes involved in the metabolism of amino acids. Further analysis by
Northern blot revealed that PPAR influences the expression of
several genes involved in trans- and deamination of amino acids, and
urea synthesis. Direct activation of PPAR using the synthetic
PPAR ligand WY14643 decreased mRNA levels of these genes, suggesting
that PPAR is directly implicated in the regulation of their
expression. Consistent with these data, plasma urea concentrations are
modulated by PPAR in vivo. It is concluded that in addition to
oxidation of fatty acids, PPAR also regulates metabolism of amino
acids in liver, indicating that PPAR is a key controller of
intermediary metabolism during fasting.—Kersten, S., Mandard, S.,
Escher, P., Gonzalez, F. J., Tafuri, S., Desvergne, B., Wahli, W.
The peroxisome proliferator-activated receptor regulates amino acid
metabolism.
Key Words: fasting • microarray • PPAR • SABRE
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