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Hanhoff, T; Wolfrum, C; Ellinghaus, P; Seedorf, U; Spener, F.
Pristanic acid is activator of peroxisome proliferator activated receptor alpha
EUR J LIPID SCI TECHNOL. 2001; 103(2): 75-80. Doi: 10.1002/1438-9312(200102)103:2<75::AID-EJLT75>3.3.CO;2-T
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Leading authors Med Uni Graz: Spener Friedrich
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Abstract:: Isoprenoid phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is degraded in peroxisomes by alpha -oxidation to pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) and then via beta -oxidation. Branched-chain phytanic add is an activator of the peroxisome proliferator activated receptor alpha (PPAR alpha) which in liver cells regulates expression of genes encoding peroxisomal and mitochondrial beta -oxidative enzymes as well as cytosolic/nuclear liver-type fatty acid binding protein (L-FABP). In this report we address the question whether pristanic acid also acts as activator of PPARa and thus mediates the expression of its catabolizing enzymes. In a first in vivo approach we fed pristanic acid for 14 days to wildtype mice and to mice lacking sterol carrier protein 2/sterol carrier protein x which leads to a phenotype having high concentrations of branched-chain fatty acids. In either genotype, feeding pristanic acid was associated with a strong induction of peroxisomal beta -oxidation enzymes tested (acyl-CoA oxidase, bifunctional enzyme, thiolase) as well as of L-FABP. The link between pristanic acid and protein expression observed was established by carrying out assays for transactivation of PPAR alpha(. in transfected HepG2 cells. In comparison to hypolipidemic drugs and to straight-chain fatty acids known to be PPAR alpha. agonists, branched-chain phytanic and pristanic acids were substantially stronger activators, pristanic acid being even superior to phytanic acid.
Find related publications in this database (Keywords): fatty acid binding protein; peroxisomal beta-oxidation; phytanic acid; peroxisome proliferator activated receptor alpha; pristanic acid