ω-3 Fatty acids reverse lipotoxity through induction of autophagy in nonalcoholic fatty liver disease

Objective: The aim of this study was to evaluate the effect of omega-3 fatty acids on nonalcoholic fatty liver disease concerning hepatocyte lipid accumulation as well as apoptosis induced by free fatty acids (FFAs) and to explore the underlying mechanism involving autophagy. Methods: Hepatocytes were incubated with a mixture of free fatty acids (FFAs) to mimic in vitro lipotoxicity in the pathogenesis of nonalcoholic fatty liver disease, presented by lipid accumulation and cellular apoptosis. Chemical inhibitor or inducer of autophagy and genetic deficit cells, as well as omega-3 fatty acids were used as intervention. The autophagic role of omega-3 fatty acids was investigated using Western blot and immunofluorescence. The underlying mechanism of omega-3 fatty acids involving autophagy was preliminarily explored by quantitative real-time polymerase chain reaction and Western blot. Results: FFAs induce lipid accumulation and apoptosis in hepatocytes. Inhibition or genetic defect of autophagy increases lipid accumulation induced by FFA, whereas induction acts inversely. omega-3 Fatty acids reduced lipid accumulation and inhibited apoptosis induced by FFA. omega-3 Fatty acids induced autophagy by downregulating stearoyl-CoA desaturase 1 expression in hepatocytes. Conclusion: omega-3 Fatty acids exert protective effects on hepatocytes against lipotoxicity through induction of autophagy, as demonstrated by inhibition of lipid accumulation and apoptosis. (C) 2015 Elsevier Inc. All rights reserved.