Effect of ω3 PUFA on diet induced non‐alcoholic fatty liver disease (NAFLD) development and progression in C57BL/6J mice

Abstract

The incidence of NAFLD and non‐alcoholic steatohepatitis (NASH) has increased in parallel with obesity. While both are characterized by excessive hepatic lipid accumulation, NASH is defined as hepatic inflammation with hepatocellular damage. Our goal was to examine the effect of C20–22 ω3 PUFA on diet induced NASH in LDLR−/− C57BL/6J mice. Mice consumed the Western Diet (WD) supplemented with olive oil, eicosapentaenoic acid (20:5ω3; EPA), docosahexaenoic acid (22:6 ω3; DHA) or both EPA and DHA for 16 weeks. The WD induced a severe phenotype similar to human NASH; including robust induction of hepatosteatosis, inflammation (MCP1) and fibrosis (ProCol1α1). While dietary C20–22 ω3 PUFA failed to suppress hepatic steatosis, ω3 PUFA attenuated markers of inflammation, fibrosis, and liver damage (plasma ALT, AST). The ω3 PUFA effect on inflammation & fibrosis correlated with the down regulation of multiple transcripts involved in toll‐like receptor signaling (TRL2, TRL4, CD14). Moreover, DHA was significantly more effective than EPA or the combination of EPA & DHA at suppressing markers of inflammation and fibrosis associated with NASH. Thus, dietary ω3 PUFA attenuates inflammation & fibrosis without suppressing hepatic lipid.Research Support: USDA Grant 2009‐65200‐05846