Phytanic acid and docosahexaenoic acid increase the metabolism of all-trans-retinoic acid and CYP26 gene expression in intestinal cells

Retinoids are essential for growth and cell differentiation of epithelial t issues. The effects of the food compounds phytol, the phytol metabolite phy tanic acid, and the fatty acid docosahexaenoic acid (DHA) on the retinoid s ignaling pathway in intestinal cells were studied. Phytol inhibited the for mation of all-trans-retinoic acid (RA) from dietary retinol in intestinal c ells. Phytanic acid, a known retinoic X receptor (RXR alpha) and peroxisome proliferator activating receptor (PPAR alpha) activator. also activated PP AR delta, and to a lesser degree PPAR gamma, in a transactivation assay. Ph ytanic acid had no effect on intestinal RA hydroxylase CYP26 (also named P4 50RAI) gene expression and metabolism of all-trans-RA in intestinal Caco-2 cells. However, in combination with retinoic acid receptor (RAR)-ligands (a ll-trans-RA or synthetic Am580) phytanic acid enhanced the induction of CYP 26 and RA-metabolism in comparison to treatments with all-trans-RA or Am580 alone, Also treatment with DHA did not affect CYP26 gene expression and RA -metabolism but cotreatment of the cells with DHA and all-trans-RA or Am580 enhanced the induction of CYP26, in comparison to the induction caused by all-trans-RA or Am580 alone. This study indicates that food compounds such as phytanic acid and DHA that are RXR-agonists and have an impact on intest inal CYP26 gene expression and metabolism of all-trans-RA in intestinal cel ls. (C) 2001 Elsevier Science B.V. All rights reserved.