Oxidized lipids from heated olive oil induce intestinal inflammation in Caco-2 cells: An oxidomics-based study

Abstract

Numerous scientific studies as well as the World Health Organization have suggested the Mediterranean diet as a healthy regimen, which uses olive oil as the main source of dietary lipids. However, this trend may encourage consumers to consume high amounts of heated olive oil, which contains oxidized lipids suggested to pose an inflammatory risk in emerging research. Studies investigating the inflammatory effects of dietary oxidized lipids from olive oil are scarce. Hence, we hypothesized that oxidized lipids from heated olive oil (180degreeC,10 min) may lead to intestinal inflammation. To provide molecular and biochemical insights into the regulating effects of oxidized lipids from heated olive oil on the inflammatory response, a novel comprehensive approach, oxidomics (oxidative lipidomics), was applied to (1) screen the oxidized lipids from in vitro digested heated olive oil by determining the IL-8 expression of Caco-2 cells incubated with fractions thereof; (2) identify the inflammatory effects of screened oxidized lipids by spectrum-effect correlation analysis; (3) predict the possible mechanisms of verified inflammatory oxidized lipids by Stitch network-based metabolic pathway and molecular docking analysis of inflammatory factors. Activity-guided fractionation revealed significant changes in IL-8 expression of Caco-2 cells incubated with six fractions based on a dichloromethane/hexane solvent system. Among the common GC-MS peaks of these fractions, five peaks were positively (two peaks) and negatively (three peaks) correlated with inflammatory effects. Interestingly, network-based pathway analysis confirmed that some of these oxidized lipids, such as pentadecanoic acid, regulate proinflammatory factors and downstream pathways as lipid mediators. Molecular docking analysis revealed the interactions between oxidized lipids and several proinflammatory factors, for example, NF-kappaB. This study applied the novel oxidomics approach to reveal a holistic view of the effects of oxidized lipids in olive oil on the inflammatory pathways thereby renewing the traditional understanding of the health benefits of olive oil.Copyright © 2023