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

Gloerich, Jolein; Brink, Daan M. van den; Ruiter, J. P. N.; Vlies, Naomi van; Vaz, Frédéric M.; Wanders, Ronald J. A.; Ferdinandusse, Sacha

doi:10.1194/jlr.m600050-jlr200

Cited by 48 publications

(42 citation statements)

References 64 publications

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“…In the liver of PPAR␣-null mice, the basal expression levels of FALDH were low, about a fifth to a tenth of that in the corresponding tissue of wild-type mice, and a small but significant induction by sesame was observed. These results indicated that the induction of FALDH expression by sesame is dependent on the expression of PPAR␣, which is consistent with a recent publication (16). The sesame seeds may contain a natural ligand for PPAR␣ (3).…”

Section: Faldh Was Induced In the Liver Of Normal Mice Fed Sesame Butsupporting

confidence: 92%

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Dual Subcellular Localization in the Endoplasmic Reticulum and Peroxisomes and a Vital Role in Protecting against Oxidative Stress of Fatty Aldehyde Dehydrogenase Are Achieved by Alternative Splicing

Ashibe

Hirai

Higashi

et al. 2007

Journal of Biological Chemistry

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Fatty aldehyde dehydrogenase (FALDH, ALDH3A2) is thought to be involved in the degradation of phytanic acid, a saturated branched chain fatty acid derived from chlorophyll. However, the identity, subcellular distribution, and physiological roles of FALDH are unclear because several variants produced by alternative splicing are present in varying amounts at different subcellular locations. Subcellular fractionation experiments do not provide a clear-cut conclusion because of the incomplete separation of organelles. We established human cell lines heterologously expressing mouse FALDH from each cDNA without tagging under the control of an inducible promoter and detected the variant FALDH proteins using a mouse FALDHspecific antibody. One variant, FALDH-V, was exclusively detected in peroxisomal membranes. Human FALDH-V with an amino-terminal Myc sequence also localized to peroxisomes. The most dominant form, FALDH-N, and other variants examined, however, were distributed in the endoplasmic reticulum. A gas chromatography-mass spectrometry-based analysis of metabolites in FALDH-expressing cells incubated with phytol or phytanic acid showed that FALDH-V, not FALDH-N, is the key aldehyde dehydrogenase in the degradation pathway and that it protects peroxisomes from oxidative stress. In contrast, both FALDHs had a protective effect against oxidative stress induced by a model aldehyde for lipid peroxidation, dodecanal. These results suggest that FALDH variants are produced by alternative splicing and share an important role in protecting against oxidative stress in an organelle-specific manner.Plants produce a variety of secondary metabolites, and some of these are potentially toxic to animals (1). Herbivora have developed behavioral and physiological strategies to avoid specific plants and to detoxify any toxins ingested. Detoxification can occur in the mouth and the gut rumen with or without the help of microbes (2). The absorbed toxins must be detoxified in the intestine and liver, but studies on these mechanisms are limited because to date most animal experiments have been carried out using laboratory diets. Recently we found that a nuclear receptor, peroxisome proliferator-activated receptor ␣ (PPAR␣), 2 is involved in the detoxification by using plant seeds as a diet for mice (3).PPAR␣ is activated by fatty acid ligands and is an important regulator of lipid metabolism in animals (4). Despite the claimed essential role of this receptor in the liver, the PPAR␣-null mouse shows little phenotypic change when fed a normal laboratory diet (5, 6). We have examined its extrahepatic roles and found that PPAR␣ induces the expression of 17␤-hydroxysteroid dehydrogenase type 11 in the intestine (7). Recent studies on the substrates of 17␤-hydroxysteroid dehydrogenase type 11 showed that they include not only glucocorticoids and sex steroids but also bile acids, fatty acids, and branched amino acids (8, 9). So we examined the possibility that PPAR␣ plays a vital role in inducing enzymes for metabolizing secondary metabolites...

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Section: Faldh Was Induced In the Liver Of Normal Mice Fed Sesame Butsupporting

confidence: 92%

“…The expression of all the mRNAs was largely induced in mouse liver upon administration of a PPAR␣ agonist. Gloerich et al (16) recently found that the conversion of phytol to phytanic acid is regulated via PPAR␣ using null mice. The present observations support their conclusion.…”

Section: Faldh Was Induced In the Liver Of Normal Mice Fed Sesame Butmentioning

confidence: 99%

Dual Subcellular Localization in the Endoplasmic Reticulum and Peroxisomes and a Vital Role in Protecting against Oxidative Stress of Fatty Aldehyde Dehydrogenase Are Achieved by Alternative Splicing

Ashibe

Hirai

Higashi

et al. 2007

Journal of Biological Chemistry

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“…We wished to know whether GGOH is oxidized to GGA in human cells, because GGA has been shown to be a biologically active compound that can induce cell death in human hepatoma cells (16). In the literature, enzymatic conversion of phytol to phytanic acid has been highly scrutinized to explore pathogenesis of Refsum disease (4,15,23). Phytol and dihydrophytol are oxidized to phytenal and phytanal, respectively, by mitochondrial alcohol dehydrogenase; both aldehydes are further oxidized to phytenoic acid and phytanic acid by mitochondrial/ microsomal fatty aldehyde dehydrogenase.…”

Section: Preparation Of Lipid Extracts From Huh-7 Cellsmentioning

confidence: 99%

Geranylgeraniol oxidase activity involved in oxidative formation of geranylgeranoic acid in human hepatoma cells

Mitake

Shidoji

2012

Biomed. Res.

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Geranylgeranoic acid (GGA), a 20-carbon acyclic polyprenoic acid (all-trans 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecatetraenoic acid) and its derivatives were developed as synthetic "acyclic retinoids" for cancer chemoprevention. Previously, we have shown the natural occurrence of GGA in various medicinal herbs and reported enzymatic formation of GGA from geranylgeraniol (GGOH) through geranylgeranial (GGal) by rat liver homogenates. Here, we present several lines of evidence that a putative GGOH oxidase is involved in GGA synthesis by human hepatoma cell lysates. First, conversion of GGOH to GGal did not require exogenous NAD +

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“…A previous study showed that phytanic acid had cytotoxic effects on the mitochondria and stellate cells in the rat brain (Schönfeld et al, 2006). However, both phytanic and pristane acids play a regulatory role in adipocyte differentiation and polyester, glucose, and lipid metabolism (Heim, 2002); it can promote fatty acid b-oxidation and significantly lower liver triglyceride and plasma fatty acids (Gloerich et al, 2007). In this study, both commercial pellet feed-feeding and small trash fish-feeding crabs contained high levels of phytanic acid, suggesting that crab is similar to other high phytanic acid foods and may have potential health functions.…”

Section: Phytanic Acidmentioning

confidence: 99%

Fatty acid composition evaluation of edible parts of Eriocheir sinensis in intensive ponds of Gucheng waters

Yan

2015

Genet. Mol. Res.

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ABSTRACT. In Gucheng Lake, Jiangsu Province, China, randomly selected crabs were fed 2 diet types. Crab crude oil methyl ester analysis was performed using gas chromatography-mass spectrometry. Fatty acid compositions in the 3 edible parts of a crab -the hepatopancreas, gonad, and muscle -were analyzed. C16:1 and C18:2 were significantly higher in most commercial pellet feed-feeding crabs than in small trash fish-feeding crabs, while the opposite was observed for eicosapentaenoic and docosahexaenoic acids. Phytanic acid reached 1.93% in the hepatopancreas of small trash fish-feeding crabs. Furan fatty-acid-DiMe (11,5) contents in the testes of small trash fish-feeding crabs was 1.49%. These values were higher in male crabs than in female crabs. According to a standard ratio of 1:1:1 which meaning the saturated fathy acid (SFA), monounsaturated fatty acid (MUFA), and polyunsaturated fatty acid (PUFA) were 33.33 each, fatty acid structure analysis of crab edible parts showed that SFA:MUFA:PUFA of crab edible parts was 2.3-4.1:2.9-5.0:1.3-4.8. The highest muscle score was 29.53 in male trash fish-feeding crabs, and the lowest hepatopancreas score was -40.81 in female commercial pellet feed-feeding crabs. The (2015) n-6/n-3 ratio was 0.36-2.48. Muscle ratio was the lowest in female commercial pellet feed-feeding crabs. Thus, small trash fish-feeding and commercial pellet feed-feeding crabs are healthy foods. Overall, for consumption, the males of small trash fish-feeding crabs were better than the females, the muscle was better than the gonads and hepatopancreas, and the testis was better than the ovary.

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

Cited by 48 publications

References 64 publications

Dual Subcellular Localization in the Endoplasmic Reticulum and Peroxisomes and a Vital Role in Protecting against Oxidative Stress of Fatty Aldehyde Dehydrogenase Are Achieved by Alternative Splicing

Dual Subcellular Localization in the Endoplasmic Reticulum and Peroxisomes and a Vital Role in Protecting against Oxidative Stress of Fatty Aldehyde Dehydrogenase Are Achieved by Alternative Splicing

Geranylgeraniol oxidase activity involved in oxidative formation of geranylgeranoic acid in human hepatoma cells

Fatty acid composition evaluation of edible parts of Eriocheir sinensis in intensive ponds of Gucheng waters

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