Supplementation of Folic Acid Attenuates Hepatic Inflammation in High Fat Diet Fed Mice

Non‐alcoholic fatty liver disease (NAFLD) is a chronic hepatic disorder associated with obesity. One major hallmark of NAFLD that impacts pathogenesis of simple steatosis progression to non‐alcoholic steatohepatitis (NASH) is inflammation. Micronutrient deficiency has been reported in patients with NAFLD, suggesting that vitamin supplementation may be beneficial in this disease context. Folic acid is a water soluble B‐vitamin acquired from the diet that plays a crucial role in biological functions. The objective of our study was to investigate the mechanisms by which folic acid supplementation alleviated hepatic inflammation in high fat diet (HFD) fed mice. Mice were fed a control diet (10% kcal of fat), high fat diet (60% kcal of fat) or high fat diet supplemented with folic acid. Histological analysis in liver tissue revealed increased aggregation of inflammatory foci following HFD feeding. Furthermore, the binding activity of pro‐inflammatory transcription factor nuclear factor‐kappa B (NF‐κB) was significantly elevated in HFD liver tissue. This correlated with enhanced expression of downstream pro‐inflammatory cytokines. Folic acid supplementation attenuated HFD‐induced hepatic inflammatory response via inhibiting NF‐κB activation. Our results suggest that HFD feeding contributes to hepatic inflammation. The hepatoprotective effect of folic acid is attributed, in part, to its anti‐inflammatory action. Funding Source: Natural Sciences and Engineering Research Council of Canada