Influence of the nutritional status and oxidative stress in the desaturation and elongation of n-3 and n-6 polyunsaturated fatty acids: Impact on non-alcoholic fatty liver disease

Abstract

Polyunsaturated fatty acids (PUFA) play essential roles in cell membrane structure and physiological processes including signal transduction, cellular metabolism and tissue homeostasis to combat diseases. PUFA are either consumed from food or synthesized by enzymatic desaturation, elongation and peroxisomal β-oxidation. The nutritionally essential precursors α-linolenic acid (C18:3n-3; ALA) and linoleic acid (C18:2n-6; LA) are subjected to desaturation by Δ6D/Δ5D desaturases and elongation by elongases 2/5, enzymes that are induced by insulin and repressed by PUFA. Maintaining an optimally low n-6/n-3 PUFA ratio is linked to prevention of the development of several diseases, including nonalcoholic fatty liver disease (NAFLD) that is characterized by depletion of PUFA promoting hepatic steatosis and inflammation. In this context, supplementation with n-3 PUFA revealed significant lowering of hepatic steatosis in obese patients, whereas prevention of fatty liver by high-fat diet in mice is observed in n-3 PUFA and hydroxytyrosol co-administration. The aim of this work is to review the role of nutritional status and nutrient availability on markers of PUFA biosynthesis. In addition, the impact of oxidative stress developed as a result of NAFLD, a redox imbalance that may alter the expression and activity of the enzymes involved, and diminished n-3 PUFA levels by free-radical dependent peroxidation processes will be discussed.