Dietary regulation of inflammatory response in non-alcoholic fatty liver disease

Background: Non-alcoholic fatty liver disease (NAFLD) is a broad spectrum liver disorder that ranges from steatosis to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The manifestation of NAFLD often coexists with abnormalities of the metabolic disorders including diabetes, obesity, hyperlipidemia and high blood pressure. Chronic hepatic inflammation is an important pathological feature of NAFLD and contributes to low-grade systemic inflammation, which, in turn, enhances cardiovascular risk. The primary cause of mortality in NAFLD patients is coronary artery disease. There is currently no pharmacological agent approved from therapeutic 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.
Methods/Results: 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 5-8 weeks. High-fat diet feeding induced a significant body weight gain, as well as increased aggregation of inflammatory foci and lipid vacuoles in the liver. Hepatic lipid accumulation and inflammatory cell aggregation were examined by hematoxylin and eosin (H&E) staining in liver tissue.
Folic acid supplementation reduced the number of inflammatory foci and lipid vacuoles in the liver. This correlated with reduced expression of pro-inflammatory cytokines mediated through attenuation of nuclear factor-κB (NF-κB) activity, an essential transcriptional regulator of inflammatory genes. Folic acid supplementation did not alter the body weight of high-fat diet fed mice.
Conclusions: Our study demonstrates that folic acid supplementation can attenuate the hepatic inflammatory response induced by high-fat diet. The anti-inflammatory effects of folic acid suggests that supplementation of this vitamin may have therapeutic implications for the management of NAFLD and reduction of cardiovascular risk associated with metabolic disorders.