Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Wolfrum, C; Ellinghaus, P; Fobker, M; Seedorf, U; Assmann, G; Börchers, T; Spener, F.
Phytanic acid is ligand and transcriptional activator of murine liver fatty acid binding protein.
J Lipid Res. 1999; 40(4):708-714
Doi: 10.1016/S0022-2275(20)32150-7
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- Führende Autor*innen der Med Uni Graz
- Spener Friedrich
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- Abstract:
- Branched-chain phytanic acid is metabolized in liver peroxisomes. Sterol carrier protein 2/sterol carrier protein x (SCP2/SCPx) knockout mice, which develop a phenotype with a deficiency in phytanic acid degradation, accumulate dramatically high concentrations of this fatty acid in serum (Seedorf at al. 1998. Genes Dev. 12: 1189-1201) and liver. Concomitantly, a 6.9-fold induction of liver fatty acid binding protein (L-FABP) expression is observed in comparison to wild-type animals fed standard chow, possibly mediated by the peroxisome proliferator-activated receptor alpha (PPARalpha). Cytosolic transport of phytanic acid to either peroxisomal membranes or to the nucleus for activation of PPARalpha may be mediated by L-FABP, which gives rise to the question whether phytanic acid is a transactivator of this protein. Here we show first that phytanic acid binds to recombinant L-FABP with high affinity. Then the increase of the in vivo phytanic acid concentration by phytol feeding to mice results in a 4-fold induction of L-FABP expression in liver, which is in the order of that attained with bezafibrate, a known peroxisome proliferator. Finally to test in vitro whether this induction is conferred by phytanic acid, we cotransfected HepG2 cells with an expression plasmid for murine PPARalpha and a CAT-reporter gene with 176 bp of the murine L-FABP promoter, containing the peroxisome proliferator responsive element (PPRE). After incubation with phytanic acid, we observed a 3.2-fold induction of CAT expression. These findings, both in vivo and in vitro, demonstrate that phytanic acid is a transcriptional activator of L-FABP expression and that this effect is mediated via PPARalpha.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antilipemic Agents - pharmacology
- Bezafibrate - pharmacology
- Carrier Proteins - genetics Carrier Proteins - metabolism
- Cell Line -
- Chloramphenicol O-Acetyltransferase - genetics
- DNA, Complementary -
- Escherichia coli - genetics
- Fatty Acid-Binding Proteins -
- Gene Expression - drug effects
- Liver - metabolism
- Mice -
- Myelin P2 Protein - genetics Myelin P2 Protein - metabolism
- Neoplasm Proteins -
- Nerve Tissue Proteins -
- Phytanic Acid - metabolism Phytanic Acid - pharmacology
- Phytol - pharmacology
- Rats -
- Receptors, Cytoplasmic and Nuclear - genetics
- Recombinant Proteins - metabolism
- Transcription Factors - genetics
- Transcription, Genetic - drug effects
- Transcriptional Activation -
- Transfection -
- Find related publications in this database (Keywords)
- peroxisome proliferator-activated receptor
- peroxisome proliferation
- sterol carrier protein 2
- sterol carrier protein x
- isothermal titration calorimetry SCP2/SCPx-deficient knock out mice
- L-FABP