Pristanic acid is activator of peroxisome proliferator activated receptor alpha

Isoprenoid phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is degrad ed in peroxisomes by alpha -oxidation to pristanic acid (2,6,10,14-tetramet hylpentadecanoic acid) and then via beta -oxidation. Branched-chain phytani c add is an activator of the peroxisome proliferator activated receptor alp ha (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 i n vivo approach we fed pristanic acid for 14 days to wildtype mice and to m ice lacking sterol carrier protein 2/sterol carrier protein x which leads t o a phenotype having high concentrations of branched-chain fatty acids. In either genotype, feeding pristanic acid was associated with a strong induct ion of peroxisomal beta -oxidation enzymes tested (acyl-CoA oxidase, bifunc tional enzyme, thiolase) as well as of L-FABP. The link between pristanic a cid and protein expression observed was established by carrying out assays for transactivation of PPAR alpha(. in transfected HepG2 cells. In comparis on to hypolipidemic drugs and to straight-chain fatty acids known to be PPA R alpha. agonists, branched-chain phytanic and pristanic acids were substan tially stronger activators, pristanic acid being even superior to phytanic acid.