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

Kersten, S; Mandard, S; Escher, Pascal; Gonzalez, F J; Tafuri, S; Desvergne, B; Wahli, W (2001). The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism. FASEB journal, 15(11), pp. 1971-1978. Federation of American Societies for Experimental Biology 10.1096/fj.01-0147com

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Escher, Pascal

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

PD Dr. Pascal Escher

Date Deposited:

11 Jul 2017 08:40

Last Modified:

31 Jul 2017 08:31

Publisher DOI:

10.1096/fj.01-0147com

PubMed ID:

11532977

URI:

https://boris.unibe.ch/id/eprint/101782

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