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 alpha (PPARalpha). To investigate the metabolism of phytol and the role of PPARalpha in its regulation, wild-type and PPARalpha knockout (PPARalpha-/-) mice were fed a phytol-enriched diet or, for comparison, a diet enriched with Wy-14,643, a synthetic PPARalpha 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 PPARalpha-/- mice compared with wild-type mice. Activity measurements of the enzymes involved in phytol metabolism showed that treatment with a PPARalpha agonist resulted in a PPARalpha-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 PPARalpha and is specific for the breakdown of (E)-phytol.
Highlights
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 a (PPARa)
Our results show that PPARa plays an important role in the regulation of the enzymes involved in phytol degradation
In livers from PPARa2/2 mice, phytol was found to accumulate to much higher levels compared with livers from wild-type animals upon longer duration of the phytol-enriched diet, suggesting a decreased capacity for phytol metabolism in PPARa2/2 mice compared with wild-type animals
Summary
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 a (PPARa). Addition of phytol to the diet results in an increase of phytol metabolites in tissues and plasma [6, 11,12,13] This has been used as a model to study the effects of the accumulation of phytol metabolites on fatty acid metabolism, in particular via the activation of the nuclear hormone receptor peroxisome proliferator-activated receptor a (PPARa), which is an important transcription factor in the regulation of fatty acid metabolism. Both phytanic and pristanic acid have been shown to activate PPARa in vitro [14, 15], and more recently, PPARa was shown to be activated in vivo in mice fed a phytol-enriched diet [13].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
