Omega-3 fatty acids and metabolic partitioning of fatty acids within the liver in the context of nonalcoholic fatty liver disease.

Abstract

Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent form of liver disease globally, affecting about 25% of the world's adult population. It is more common in those living with obesity, where it may affect as many as 80% of individuals. The aim of this article is to describe recent human studies evaluating the influence of omega-3 fatty acids on de novo lipogenesis (DNL) and hepatic fatty acid partitioning between incorporation into triacylglycerols (TAGs) and β-oxidation, to discuss the relevance of these effects in the context of NAFLD, and to provide an overview of the mechanisms that might be involved. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease hepatic DNL and partition fatty acids away from TAG synthesis and toward β-oxidation. EPA and DHA affect multiple hepatic transcription factors resulting in down-regulation of the DNL pathway and upregulation of β-oxidation. The net result is decreased accumulation of hepatic TAG and lowering of circulating TAG concentrations. Human trials demonstrate that EPA and DHA can decrease liver fat in patients with NAFLD. Increased intake of EPA and DHA may reduce the likelihood of hepatic TAG accumulation and could be used to reduce liver fat in patients with NAFLD.