Oxidative stress and depletion of hepatic long-chain polyunsaturated fatty acids may contribute to nonalcoholic fatty liver disease.

Human nonalcoholic fatty liver disease (NAFLD) associated with obesity is characterized by depletion of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFA), with lower LCPUFA product/precursor ratios and higher 18:1n-9 trans levels in adipose tissue, both in patients with steatosis and in those with steatohepatitis. These changes point to modification of gene expression, with decreased fatty acid oxidation and triacylglycerol export and enhanced lipid synthesis, thereby leading to fat accumulation in the liver. Changes in oxidative stress-related parameters indicate a moderate enhancement in the pro-oxidant status of the liver in steatosis, which is further exacerbated in steatohepatitis. It is proposed that oxidative stress plays a dual role in NAFLD by contributing to steatosis due to higher peroxidation of LCPUFA, in addition to defective fatty acid desaturation and diet imbalance, and by promoting progression of steatosis to steatohepatitis, features that might involve changes in the activity of transcriptional mediators.