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

• DOI: 10.1194/jlr.m600050-jlr200
• Publication Date: 2006-10-03T00:40:23Z
• Authors: J. Gloerich; D.M. van den Brink; J. P.N. Ruiter; N. van Vlies; F.M. Vaz; R. J.A. Wanders; S. Ferdinandusse
• Keywords: Phytanic acid; Phytol

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