Perturbation of lipid metabolism by linoleic acid hydroperoxide in CaCo-2 cells.
Dietary hydroperoxides are being discussed as potential health hazards contributing to oxidative stress-related diseases. However, how food-born hydroperoxides could exert systemic effects remains elusive in view of the limited chances to be absorbed. Therefore, the metabolic fate of 13-HPODE (13-hydroperoxy octadecadienoic acid), 13-HODE (13-hydroxy octadecadienoic acid) and linoleic acid (LA) was investigated in a CaCo-2 cell monolayer as a model of the intestinal epithelium. [1-14C]-13-HPODE, up to a non-cytotoxic concentration of 100 microM, did not cross the CaCo-2 cell monolayer unreduced if applied to the luminal side. The [1 -14C]-HPODE-derived radioactivity was preferentially recovered from intracellular and released diacylglycerols (DG), phospholipids (PL) and cholesterol esterified with oxidized fatty acids (oxCE). A similar distribution pattern was obtained with 13-HODE. In contrast, LA is preferentially incorporated into triacylglycerols (TG), cholesteryl esters (CE) and PL (but mainly released as TG). 13-HPODE dose-dependently decreased the incorporation of LA into released TG, while LA accumulated in cellular and released DGs, effects similarily exerted by 13-HODE. We concluded that food-born hydroperoxy fatty acids are instantly reduced by the gastrointestinal glutathione peroxidase, which was previously shown to persist in selenium deficiency. Accordingly, modulation of the glutathione peroxidases by selenium deprivation/repletion did not modify the disturbance of the lipid metabolism by 13-HPODE. Thus, hydroperoxy fatty acids disturb intestinal lipid metabolism by being esterified as hydroxy fatty acids into complex lipids, and may render lipoproteins synthesized thereof susceptible to further oxidative modifications.
Müller
Cordula
C
German Institute of Human Nutrition, University of Potsdam, Bergholz-Rehbrücke.
Friedrichs
Bärbel
B
Wingler
Kirstin
K
Brigelius-Flohé
Regina
R
D001692:Biological Transport; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D006801:Humans; D008041:Linoleic Acids / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D011865:Radioisotope Dilution Technique
D002250:Carbon Radioisotopes; D008041:Linoleic Acids; D008054:Lipid Peroxides; C038649:13-hydroperoxy-9,11-octadecadienoic acid; C008285:linoleic acid hydroperoxide; C024348:13-hydroxy-9,11-octadecadienoic acid