Regulation of hepatic inflammation by folic acid in non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum liver disorder that ranges from steatosis to steatohepatitis, cirrhosis and hepatocellular carcinoma. The histopathology of NAFLD is characterized by steatosis, inflammation, fibrosis, and liver injury. Chronic hepatic inflammation is an important feature of NAFLD that contributes to pathogenesis of the disease. There is currently no pharmacological agent approved for treatment of NAFLD. Dietary supplementation of vitamins is important for health maintenance, and has been suggested to be a beneficial strategy for NAFLD management. Folic acid is a water-soluble B vitamin that has been demonstrated to have lipid-lowering and anti-oxidant effects. The objective of our study was to investigate the effects of folic acid supplementation on hepatic inflammation and to identify the underlying mechanisms. Male C57Bl/6J mice were fed a control diet (10% kcal fat), a high-fat diet (60% kcal fat), or a high-fat diet supplemented with folic acid (26mg/kg diet) for a 5-8 week period. Folic acid supplementation reduced the aggregation of inflammatory foci as well as lipid accumulation in the liver induced by high-fat diet consumption. This correlated with reduced expression of pro-inflammatory cytokines mediated through inhibition of NF-κB transcription activity, an inflammatory transcriptional regulator. Folic acid supplementation did not alter the body weights of mice fed a high-fat diet. Our results suggest that folic acid supplementation can attenuate the hepatic inflammatory response induced by chronic consumption of a high-fat diet, which may contribute to the hepatoprotective effect by folic acid.