Dietary docosahexaenoic acid reverses nonalcoholic steatohepatitis and fibrosis caused by conjugated linoleic acid supplementation in mice

It has been shown that docosahexaenoic acid (DHA) prevents nonalcoholic fatty liver disease (NAFLD) and insulin resistance (IR) caused by conjugated linoleic acid (CLA), a trans fatty acid (TFA). Here, we evaluated whether DHA will reverse existing CLA-induced NAFLD and IR in mice. DHA-specific effects on existing NAFLD involved significant (P <0.005) lowering of hepatic weight and triacylglycerol content and expression of genes involved in fatty acid synthesis, enhancing expression of genes involved in fatty acid oxidation, and increasing serum adiponectin levels. Also, immunohistochemistry showed lower expression of hepatic CD163 (inflammation) and smooth muscle α-actin (fibrosis). Compared to the CLA diet, mice fed DHA and control diets had significantly (P <0.05) lower serum insulin and ALT activity, but only DHA had lower (P = 0.05) expression of genes involved in fibrosis. DHA supplementation for 4 weeks reversed already existing hepatic steatosis, inflammation, and fibrosis caused by CLA.