A lipidomic analysis of nonalcoholic fatty liver disease (NAFLD) reveals significant changes in the lipid composition of the liver. The study compared lipid levels in normal livers, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Key findings include increased levels of diacylglycerol (DAG) and triacylglycerol (TAG) in NAFLD, with a stepwise increase in the TAG/DAG ratio from normal to NAFL to NASH. Free fatty acid (FFA) levels remained unchanged, while free cholesterol (FC) increased, leading to a higher FC/phosphatidylcholine (PC) ratio. Total PC decreased in both NAFL and NASH, and there was a progressive depletion of n-6 and n-3 fatty acids in TAG, with a significant increase in the n-6:n-3 ratio in NASH. The study also found reduced levels of arachidonic acid and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in NASH, suggesting impaired fatty acid metabolism. These lipid changes may contribute to the progression of NAFLD to NASH. The findings highlight the importance of lipid composition in the pathophysiology of NAFLD and suggest potential therapeutic targets, such as n-3 fatty acid supplementation for NASH treatment. The study underscores the need for further research to understand the complex biological implications of these lipid changes.A lipidomic analysis of nonalcoholic fatty liver disease (NAFLD) reveals significant changes in the lipid composition of the liver. The study compared lipid levels in normal livers, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH). Key findings include increased levels of diacylglycerol (DAG) and triacylglycerol (TAG) in NAFLD, with a stepwise increase in the TAG/DAG ratio from normal to NAFL to NASH. Free fatty acid (FFA) levels remained unchanged, while free cholesterol (FC) increased, leading to a higher FC/phosphatidylcholine (PC) ratio. Total PC decreased in both NAFL and NASH, and there was a progressive depletion of n-6 and n-3 fatty acids in TAG, with a significant increase in the n-6:n-3 ratio in NASH. The study also found reduced levels of arachidonic acid and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in NASH, suggesting impaired fatty acid metabolism. These lipid changes may contribute to the progression of NAFLD to NASH. The findings highlight the importance of lipid composition in the pathophysiology of NAFLD and suggest potential therapeutic targets, such as n-3 fatty acid supplementation for NASH treatment. The study underscores the need for further research to understand the complex biological implications of these lipid changes.