Oxidized food lipids regulating lipid metabolism

Consumption of foods rich in polyunsaturated fatty acids is considered healthy. At the same time, Western diet is characterized by intake of processed foods. However, polyunsaturated fatty acids are easily converted to oxidized lipids during food processing and storage. Despite traditional cooking techniques by exposing food to heat prior to consumption, scientific studies investigating the effect of heated food lipids on human health are scarce. Previous reports indicate regulations of lipid metabolism by oxidized lipids in obese and diabetic subjects. However, it is not yet known which oxidized lipids are formed in foods and influence the energy metabolism after digestion and absorption. In the current project, the generation of oxidized lipids in foods, their fate during digestion, absorption and metabolization as well as their effects on lipid metabolism will be investigated. As the lipid metabolism is associated with the mobility of the lipids in the cell membrane, the so-called membrane fluidity, nutrient transport through membrane receptors might be influenced by oxidized lipids. We, therefore, also aim to investigate the effects of oxidized lipids on glucose and fatty acid uptake as well as lipid accumulation in heart and liver cells as well as in mini-organs, so-called liver organoids. By showing differential effects of oxidized and unoxidized lipids on the lipid metabolic pathways the project could identify lipid compounds exerting detrimental and beneficial effects on the lipid metabolism. The project results will reveal cooking techniques which promote formation of oxidized lipids in foods with detrimental effects on the energy metabolism and how the generation of these oxidized lipids can be inhibited. Unlike previous approaches, we want to cover oxidation products from its appearance in food, thereby also considering their digestion and absorption, to the influences on lipid metabolic pathways. It will break new ground in research if a link to metabolic dysfunction, such as diabetes and obesity, can be established.

Consumption of foods rich in polyunsaturated fatty acids is considered healthy. At the same time, Western diet is characterized by the intake of processed foods. This may represent an issue, as polyunsaturated fatty acids are easily converted to oxidized lipids during food processing and storage. Despite common processing and cooking techniques exposing food to heat prior to consumption, the full range of oxidized lipids that can be generated in the process is yet to be explored. Furthermore, the fate and impact of oxidized lipids in the human body remains poorly understood, scarcely covered by previous research. Thus, the current project aimed to bring answers to these gaps by taking a holistic approach, going from characterizing oxidized lipids in food as well as trying to limit their formation, to investigating the meaning of their presence during digestion, absorption and metabolism. Using advanced analytical techniques, such as mass spectrometry, oxidized lipids from different cold-pressed vegetable oils were determined, and a systematic, multi-marker model that allowed the robust identification of biomarkers for oil deterioration was successfully built. Strategies to improve the oxidative stability of these oils were then investigated. Among them, certain procedures such as green extraction and seed germination proved to be effective techniques to obtain oils with reduced amounts of oxidized lipids, which entails a longer shelf life, a positive characteristic to reduce food waste. To identify the fate of oxidized lipids after their intake, in vitro (cells) and in vivo (animal) models were utilized. Our research found that oxidation products derived from linoleic acid, an omega-6 fatty acid, can influence the expression of transporter proteins in enterocytes (a type of intestinal cells), suggesting a direct impact on lipid absorption. Subsequent research evaluated the pro-inflammatory impact of epoxidized triacylglycerols, a class of oxidized lipids, and products from their digestion in enterocyte cells models. This led to the discovery of novel digestion products called chlorohydrins, indicating their potential contribution to intestinal inflammation. Moreover, an epoxidized fatty acid was identified as novel pro-inflammatory lipid mediator in mice, suggesting the relevance of these oxidation products in vivo. Overall, the current project provided a deeper understanding on the mechanisms behind lipid oxidation and provided practical strategies for the extension of the shelf-life of oils rich in polyunsaturated fatty acids. On top of that, the project lead to the identification of several novel pro-inflammatory markers, giving molecular insights into the biological fate of oxidized dietary lipids and offering potential implications for developing dietary guidance to promote human health.