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Effects of n3/n6‐Derived Epoxy‐Fatty Acids on Hepatocyte Cell Death

Epoxy‐fatty acids (EpFAs) are bioactive lipid mediators that are derived from n3‐ and n6‐polyunsaturated fatty acids (PUFAs) via CYP450 epoxygenation. EpFAs are thought to be beneficial lipids by virtue of their systemic anti‐inflammatory, anti‐fibrotic, and tissue‐regenerative effects. EpFAs are endogenously deactivated by soluble epoxide hydrolase (sEH) to their less biologically active, or in some cases deleterious, dihydroxy‐fatty acid (dihydroxy‐FAs). Recent work from our group discovered an imbalance in the EpFA/dihydroxy‐FA pool in patients with alcohol‐associated liver disease (ALD). Importantly, little is known regarding the mechanisms associated with this imbalance or the role of individual EpFAs or dihydroxy‐FAs in ALD. Therefore, the objective of this study was to interrogate the effects of EpFAs and dihydroxy‐FAs on hepatocyte cell death, a key pathological contributor to liver injury in ALD.