Phytol and Peroxisome Proliferation

Abstract

ABSTRACT. Infantile Refsum's disease is characterized by high levels of phytanic acid and the absence of normal hepatic peroxisomes. We investigated the in vivo influence of phytol, a precursor of phytanic acid, on peroxisomes by both biochemical and morphological methods. Enhanced supply of phytol in the diet of adult mice causes proliferation of hepatic peroxisomes. The peroxisomal &oxidizing capacity as well as exchanges of acyl moieties between peroxisomes and mitochondria are raised around 5-and 2-fold, respectively. In parallel a 1.5-fold increase of total catalase and mitochondria1 butyryl-CoA dehydrogenase activities occurs, whereas peroxisomal urate oxidase and glycolate oxidase remain normally active. Serum triglyceride levels are decreased after 3 wk of phytol feeding; serum cholesterol levels remain unaffected. Phytol feeding also induces peroxisome proliferation in duodenal epithelium, in myocardium and in skin sebaceous glands, but not in kidney. (Pediatr Res 20: 41 1-415, 1986)

Peroxisomal Proliferation in Heart and Liver of Mice Receiving Chlorpromazine, Ethyl 2(5(4-Chlorophenyl)Pentyl) Oxiran-2-Carboxylic Acid or High Fat Diet: A Biochemical and Morphometrical Comparative Study

“…Fahimi et al (39) have demonstrated that ethanol in the diet was efficient enough in rats to increase myocardial catalase activity and the number of heart DAB-reactive organelles. The increase of heart peroxisomes has also been described in mice given phytol (15). With the present work, we demonstrate the parallelism that exists between the number of DAB-positive organelles and the activity and sedimentability of catalase and peroxisomal 8-oxidation.…”

Peroxisomal oxidation of L‐2‐hydroxyphytanic acid in rat kidney cortex

“…We report here a pathway in which peroxisomes are directly responsible for the conversion of L-2-hydroxyphytanic acid into 2-oxophytanic acid. This finding may corroborate the hypothesis that peroxisomes play a role in phytanic acid catabolism as previously predicted from several inherited disorders [4,5] and from the experiments of Van den Branden et al [9]. The latter authors showed that administration of phytol, a precursor of phytanic acid, induces proliferation of peroxisomes and increases the activity of fatty acylCoA oxidase in mouse tissues.…”

“…This situation contrasts with the abnormal levels of phytanic acid in patients affected by infantile Refsum disease, Zellweger's cerebrohepatorenal syndrome, rhizomelic chondrodysplasia punctata and neonatal adrenoleukodystrophy, four disorders in which peroxisomes are either absent or lacking several functions [2, 5 -81. Excess plasma phytanic acid in patients with peroxisomal dysfunction, together with the finding that mouse liver peroxisomes proliferate after feeding phytol [9], suggest a role of these organelles in the shortening of the 20-carbon-atom branched-chain fatty acid.…”

A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPARα-dependent and -independent pathways

“…Most likely, one of the phytol metabolites not only activates PPAR␣ but also another, yet unknown, transcription factor, resulting in upregulation of a subset of peroxisomal enzymes. It is unlikely that phytol-mediated peroxisome proliferation, which has been described previously (46), is involved in the increased protein levels/enzyme activity we observed, because the expression of the peroxisomal membrane protein PMP70 was not increased. This is supported by the observation that peroxisome proliferation can be achieved independently from induction of PPAR␣-regulated fatty acid ␤-oxidation genes, suggesting a separate regulation of these processes (47).…”