Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation
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...
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doaj-b815119721f64338b249701cc076ea952021-04-27T04:48:02ZengElsevierJournal of Lipid Research0022-22752007-01-014817785Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulationJ. Gloerich0D.M. van den Brink1J. P.N. Ruiter2N. van Vlies3F.M. Vaz4R. J.A. Wanders5S. Ferdinandusse6Laboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsLaboratory of Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics, Emma's Children's Hospital, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsPhytol, 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.http://www.sciencedirect.com/science/article/pii/S0022227520436387peroxisome proliferator-activated receptor αfatty aldehyde dehydrogenasebranched-chain fatty acids |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
J. Gloerich D.M. van den Brink J. P.N. Ruiter N. van Vlies F.M. Vaz R. J.A. Wanders S. Ferdinandusse |
spellingShingle |
J. Gloerich D.M. van den Brink J. P.N. Ruiter N. van Vlies F.M. Vaz R. J.A. Wanders S. Ferdinandusse Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation Journal of Lipid Research peroxisome proliferator-activated receptor α fatty aldehyde dehydrogenase branched-chain fatty acids |
author_facet |
J. Gloerich D.M. van den Brink J. P.N. Ruiter N. van Vlies F.M. Vaz R. J.A. Wanders S. Ferdinandusse |
author_sort |
J. Gloerich |
title |
Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation |
title_short |
Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation |
title_full |
Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation |
title_fullStr |
Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation |
title_full_unstemmed |
Metabolism of phytol to phytanic acid in the mouse, and the role of PPARα in its regulation |
title_sort |
metabolism of phytol to phytanic acid in the mouse, and the role of pparα in its regulation |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2007-01-01 |
description |
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. |
topic |
peroxisome proliferator-activated receptor α fatty aldehyde dehydrogenase branched-chain fatty acids |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520436387 |
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