Linoleic acid and Its Oxidized Metabolites: Exposure, Bioavailability and Brain Metabolism
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Linoleic acid and Its Oxidized Metabolites: Exposure, Bioavailability and Brain Metabolism


Linoleic acid (LA or LNA) is an omega-6 polyunsaturated fatty acid (PUFA) abundant in Western diets. As a PUFA, LA is prone to oxidation both enzymatically and non-enzymatically. Non-enzymatic oxidation involves photo-oxidation or heat induced thermal oxidation. Enzymes involved in LA oxidation are lipoxygenase, cyclooxygenase, prostaglandin dehydrogenase, cytochrome P450 and soluble epoxide hydrolase. Both enzymatic and non-enzymatic oxidation of LA generates oxidized linoleic acid metabolites (OXLAMs), which are present in high-LA oils. OXLAMs have also been reported in the mammalian cardiovascular system, immune system, circulatory system and nervous system mainly from de novo synthesis from LA in vivo. Although exposure to OXLAMs has been widely studied in fried oil, it has not been studied in other food types. Additionally, the extent of dietary contribution of OXLAMs to health is an area still under investigation. OXLAMs are abundant especially in the developing brain and the source of it there is still unknown. Furthermore, factors that could affect developmental brain LA and OXLAM concentrations are largely unknown. In this dissertation, I investigated the potential dietary exposure of OXLAMs in adults using processed potatoes and French fries as a model food that is commonly consumed and subjected to multiple processing steps. I also investigated exposure for infants through the consumption of human milk. Second, I used in vivo kinetics and tracers to study the absorption and incorporation of dietary OXLAMs, especially into the brain. I used tracers to determine the contribution of dietary LA to brain OXLAM levels and turnover. Finally, I assessed factors such as maternal obesity and typical medical interventions to understand their impacts on offspring LA and OXLAM metabolism. I found that OXLAMs are the most abundant oxidized fatty acid (oxylipin) species in potatoes, French fries and human breastmilk. Interestingly, different food processing steps could alter OXLAM formation differently, not in a continuously increased oxidation trend. Dietary OXALMs can be absorbed and incorporated into adipose, liver, and heart but not the brain. Brain OXLAMs are rapidly synthesized from LA upon entering the brain. Maternal obesity interventions such as calorie restriction and use of pravastatin could cause adverse arachidonic acid and docosahexaenoic acid metabolism in the offspring prefrontal cortex without altering the metabolism of LA or OXLAMs. Continued studies on developmental brain LA and OXLAM metabolism, in vivo gastrointestinal metabolism, and bioactivities of OXLAMs in the nervous system are needed.

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