Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation

Abstract

Phytol, a branched-chain fatty alcohol, is the naturally occurring precursor of phytanic and pristanic acid, branched-chain fatty acids that are both ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor α (PPARα). To investigate the metabolism of phytol and the role of PPARα in its regulation, wild-type and PPARα knockout (PPARα−/−) mice were fed a phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a synthetic PPARα agonist. After the phytol-enriched diet, phytol could only be detected in small intestine, the site of uptake, and liver. Upon longer duration of the diet, the level of the (E)-isomer of phytol increased significantly in the liver of PPARα−/− mice compared with wild-type mice. Activity measurements of the enzymes involved in phytol metabolism showed that treatment with a PPARα agonist resulted in a PPARα-dependent induction of at least two steps of the phytol degradation pathway in liver. Furthermore, the enzymes involved showed a higher activity toward the (E)-isomer than the (Z)-isomer of their respective substrates, indicating a stereospecificity toward the metabolism of (E)-phytol. In conclusion, the results described here show that the conversion of phytol to phytanic acid is regulated via PPARα and is specific for the breakdown of (E)-phytol.

Keywords

• peroxisome proliferator-activated receptor α
• fatty aldehyde dehydrogenase
• branched-chain fatty acids