Nonalcoholic fatty liver disease: Roles of the gut and the liver and metabolic modulation by some dietary factors and especially long-chain n-3 PUFA

Nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), is the leading cause of chronic liver disease in Western countries. NASH increases the risk for fibrosis, cirrhosis, and hepatocellular carcinoma. The mechanisms underlying the steatosis to NASH transition remain incompletely understood despite recent progress in cellular and molecular aspects. Our primary aim is to analyze recent advances in understanding deviations in hepatic fat metabolism and the implication of gut physiology and microbiota in this transition. Our second aim is to gather experimental and clinical data on the capability of long-chain n-3 PUFA (LC n-3 PUFA), including docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids to prevent or alleviate NAFLD. Our main conclusions are: (i) increasing data support a pivotal role for the gut toward NASH development; (ii) LC n-3 PUFA have often proven preventive or therapeutic effect toward NASH development in rodent models. In patients with NASH they appear to have no therapeutic effects, but they could have preventive effects, which require to define better the specific roles, modes of action, and doses of DHA and EPA.