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Alcoholic fatty liver disease (AFLD) is characterized by lipid accumulation and inflammation and can progress to cirrhosis and cancer in the liver. AFLD diagnosis currently relies on histological analysis of liver biopsies. Early detection permits interventions that would prevent progression to cirrhosisor later stages of the disease. Herein, we have conducted the first comprehensive time-course study of lipids using novel state-of-the art lipidomics methods in plasma and liver in the early stages of a mouse model of AFLD, i.e., Lieber-DeCarli diet model. In ethanol-treated mice, changes in liver tissue included up-regulation of triglycerides (TGs) and oxidized TGs and down-regulation of phosphatidylcholine, lysophosphatidylcholine, and 20-22-carbon-containing lipid-mediator precursors. An increase in oxidized TGs preceded histological signs of early AFLD, i.e., steatosis, with these changes observed in both the liver and plasma. The major lipid classes dysregulated by ethanol play important roles in hepatic inflammation, steatosis, and oxidative damage. Conclusion: Alcohol consumption alters the liver lipidome before overt histological markers of early AFLD. This introduces the exciting possibility that specific lipids may serve as earlier biomarkers of AFLD than those currently being used. (Hepatology Communications 2022;6:513-525).F atty liver disease or hepatosteatosis occurs when lipids accumulate in the liver as a result of dysregulated lipid metabolism leading to increased lipogenesis, reduced lipolysis, and lipotoxicity. (1) Lipotoxicity may potentially elicit an inflammatory response that can lead to the progression to cirrhosis and hepatocellular carcinoma. Clinically, fatty liver disease can be divided into alcoholic (AFLD) and nonalcoholic fatty liver disease (NAFLD). Both AFLD and NAFLD are generally indistinguishable using only morphological evidence, other than the distinctions applied by these etiological designations. (2) Although the prevalence of NAFLD worldwide compared to AFLD has been increasing exponentially

Per- and polyfluoroalkyl substances (PFAS) are synthetic organic compounds that over the past several years, have witnessed a dramatic increase in scientific attention. As PFAS are predominantly accumulated in plasma, monitoring individual burden levels in plasma are typically achieved via some combination of protein precipitation and/or solid phase extraction (SPE), either in online or offline modes. This work describes an updated PFAS extraction workflow, using 96-well plate technology and protein precipitation that is rapid, simple, inexpensive, and amenable for large cohort studies. In brief, plasma proteins were precipitated using methanol and the resulting centrifuged supernatant was directly analyzed using UHPLC-MS/MS. We monitored 51 PFAS, which were quantified via isotope dilution and the effectiveness of the method was demonstrated by using NIST blood-based Standard Reference Materials (SRMs). This method resulted in recoveries ranging between 70 and 89% for all analytes. The 96-well design exhibited low limits of detection and only required sample volumes of 100 µL, thus resulting in an amenable method for high-throughput plasma/serum PFAS screening. • PFAS were directly quantified in plasma and serum samples; • No SPE needed after protein precipitation; • SRMs can be used to validate PFAS measurement in plasma/serum.