Oxidized lipids from sunflower oil modulate fatty acid uptake in Caco-2 cells through regulation of fatty acid transporters

Polyunsaturated fatty acids (PUFAs) in vegetable oils are generally considered as healthy. However, they can produce oxidized lipids during processing. The health effects of these oxidized lipids are not well understood, especially how they affect fatty acid uptake in enterocytes. Here, we investigated the effects of oxidized lipids from sunflower oil, especially linoleic acid (the primary fatty acid) and its oxidation products, on fatty acid uptake by differentiated Caco-2 cells. The oxidized lipids in the polar fraction of non-heated sunflower oil significantly reduced fatty acid uptake by Caco-2 cells, however, thermal treatment (80 °C and 150 °C, 60 min) reversed this inhibitory effect, which due to the formation of oxidized triglycerides containing linoleic acid. Therefore, we hypothesized that oxidized linoleic acid may be primarily responsible for the modulation of fatty acid uptake. Our findings revealed substantial upregulation of the fatty acid uptake by 168.8 ± 10.04% and 134.4 ± 21.23% in differentiated Caco-2 cells, incubated with 10 μM 13-hydroperoxy-octadecadienoic acid (13-HpODE) and 13-hydroxyoctadecadienoic acid (13-HODE), hydroperoxidized and hydroxylated derivatives of linoleic acid, respectively, which could be attributed to their regulating effects on fatty acid transporters such as FATP2, FATP4 and IFABP. Specifically, linoleic acid, 13-HpOPE and 13-HODE upregulated the gene expression of FATP2, and 13-HpODE downregulated the gene expression of IFABP. Furthermore, 13-HODE revealed time-dependent regulations of these fatty acid transporters during incubation for 6 h. Our study reveals that the modulation of fatty acid uptake in intestinal epithelial cells by oxidized lipids from sunflower oils contributes to understanding the effects of oxidized lipids on human metabolic health. • Intake of oxidized lipids from sunflower oil is inevitable regardless of the heating. • Oxidized lipids impact fatty acid uptake in intestinal epithelial cell model. • 13-HpODE enhanced fatty acid uptake via FATP2 upregulation. • 13-HODE regulated fatty acid transporters in a time-dependent manner.