Folic Acid Supplementation Attenuates Chronic Hepatic Inflammation in High-Fat Diet Fed Mice
Citation
Sid, V., Shang, Y., Siow, Y.L., Hewage, S.M., House, J.D., Karmin, O. (2018). Folic Acid Supplementation Attenuates Chronic Hepatic Inflammation in High-Fat Diet Fed Mice. Lipids, [online] 53(7), 709-716. http://dx.doi.org/10.1002/lipd.12084
Plain language summary
Increased intake of fats in our daily diet can cause inflammation in the liver, resulting in nonalcoholic fatty liver disease (NAFLD). There is currently no drug therapy for NAFLD, which is the most common form of chronic liver disease. In this study, when mice were fed a high-fat diet for 8 weeks, they exhibited the typical biological characteristics of NAFLD: increased body weight and accumulated fat, liver damage and elevated levels of the genetic information directing the assembly of inflammatory cytokines. This was also accompanied by increased levels of genes that regulate the overall genetic activity of the inflammatory cytokine genes. In comparison, mice fed a high-fat diet with a folic acid (26mg/kg diet) supplementation did not exhibit any of the elevated levels of fat, liver damage nor increased genetic activity except for increased body weight. Folic acid is a synthetic form of folate, which is a water-soluble B-vitamin found in many food (especially leafy vegetables) and has been shown by other studies to have anti-inflammatory actions. The results of this study suggest that folic acid may have a therapeutic potential for the management of NAFLD after human trials.
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide. Hepatic inflammation is an important pathogenic mediator of NAFLD. There is currently no pharmacological agent approved for the treatment of NAFLD. Folic acid is a water-soluble B vitamin that has been shown to have lipid-lowering and antioxidant effects. The objective of this study was to investigate the effect of folic acid supplementation on hepatic inflammation and to identify the underlying mechanisms. Male C57BL/6 J mice were fed a control diet (10% kcal fat), a high-fat diet (HFD) (60% kcal fat), or a HFD supplemented with folic acid (26 mg/kg diet) for 8 weeks. HFD feeding led to increased body mass gain, lipid accumulation, activation of transcription factor nuclear factor-κB (NF-κB), and elevation of inflammatory cytokine gene expression in the liver. Folic acid supplementation attenuated hepatic lipid accumulation and aggregation of inflammatory foci induced by HFD feeding. This was associated with a significant reduction of NF-κB activation and inflammatory cytokine expression. These results suggest that the hepatoprotective effect of folic acid in NAFLD may be attributed, in part, to its anti-inflammatory action.