Oxidized metabolites of linoleic acid mediated hepatotoxicity as a potential mechanism of dietary unsaturated fat and alcohol induced liver injury: in vivo and in vitro studies (959.20)

Introduction: Dietary fat and alcohol both play an important role in the development and progression of alcoholic liver disease. The aim of the present study was to evaluate the role of linoleic acid (LA, a major unsaturated fatty acid in the Western diet), and its bioactive oxidized metabolites (OXLAMs) in alcohol-induced liver injury. Materials and Methods: In-vivo study: C57BL/6 mice were fed unsaturated (USF, corn oil enriched) fat diet containing 5% ethanol for 10 days plus a single binge ethanol administration. Liver injury and steatosis as well as 12/15 lipoxygenase and plasma OXLAM levels were evaluated. In-vitro study: HepG2 cells were exposed to LA and multiple OXLAMs. Seahorse and Cellomics analysis were performed to evaluate effects of treatments on mitochondria function, ER stress, and cell survival. Results: Significant liver injury and steatosis associated with elevated plasma OXLAM levels and hepatic 12/15 lipoxygenase, an enzyme involved in OXLAM production, were observed in response to U...