Liver RNASeq data from experimental mice fed ethanol with or without TUCB treatment.
Alcohol-associated hepatitis (AH) is a serious public health problem with limited pharmacological options. The goal of the current study was to assess the efficacy and mechanisms of the inhibition of soluble epoxide hydrolase (sEH, a lipid metabolism enzyme) in an experimental model of AH. To mimic AH, male C57BL/6J mice underwent acute-on-chronic ethanol feeding with or without the sEH inhibitor TUCB. Liver injury and steatosis were assessed. Liver epoxy- and dihydroxy-fatty acids were measured by targeted metabolomics. Whole liver standard RNA sequencing were performed, and free modified RNA bases were measured by mass spectrometry. TUCB ameliorated alcohol-induced liver injury, altered liver epoxy- and dihydroxy-fatty acids, and led to a unique hepatic transcriptional profile characterized by activation of acute phase response, phagocytosis, and G-protein coupled receptor signaling. sEH inhibition-mediated protection against liver injury was associated with rescue of pathways dysregulated by ethanol including liver inflammation and immunity. Epitranscriptomic modifications may contribute to these changes. Future studies will further explore the role of epoxy- and dihydroxy-fatty acids in mechanisms underlying ALD.