Omega 3 fatty acids and hepatic insulin resistance: focus on ER stress and mitochondrial dynamics markers

Omega 3 Poly-Unsaturated Fatty Acids (PUFA-ω3) have a protective and therapeutic role to prevent hepatic insulin resistance (IR). In this study, the protective effect was evaluated through: 1) hepatic insulin signaling pathway markers (phosphorylated protein kinase B on Ser473, pAKT/PKB); 2) endoplasmic reticulum (ER) stress marker (phosphorylated transcription factor p-eIF2α); 3) mitochondrial dynamics marker (Mitofusin 2, Mfn2). These parameters were evaluated into 3 Wistar rats groups, so treated for 6 weeks: 1- N rats, treated with a standard diet (10.6% fats); 2- L rats, treated with a high fat diet, rich in lard (40% fats); 3- F rats, treated with a high fat diet rich in fish oil, major PUFA-ω3 source (40% fats). Hepatic pAKT, p-eIF2α and Mfn2 levels were determined by western blotting analysis. L group exhibited hepatic insulin resistance (as showed by pAKT content) associated with ER stress (as showed by increased p-eIF2α content). Furthermore, we observed increased hepatic insulin sensitivity (as showed by reduced pAKT content) associated to ER stress reduction (reduced p-eIF2α content) in F group compared to L group. A fundamental role seems to be played by Mfn2, that increased in F vs L group, preventing not only mitochondrial integrity, but also eIF2α phosphorylation. In this way, fish oil may have positive effect in the prevention of ER stress and IR onset