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.