Journal Article

Impact of Omega-3 Fatty Acids on the Serum Lipidomic Profile of Patients With NAFLD

Tobin, Derek, Garbotz, Christoph, Qin, Yan

2018

Overview

Introduction: A recently performed meta-analysis of the effects of omega-3 fatty acids (O3FA: EPA and DHA) on NAFLD patients showed reduced steatosis and beneficial effects on liver enzymes. O3FA have a variety of effects including membrane fluidity maintenance by incorporation into the cell membrane phospholipids, lipid regulation via activation of nuclear receptors, anti-inflammatory effects through various pathway such as NF-kB, competition with omega-6 metabolism, and a potential role as signaling molecules and in formation of lipid rafts. Here we present lipidomic profiling of serum samples collected as part of a randomized placebo controlled study of the effects of O3FA administration in patients with NAFLD. Methods: 172 subjects with ultrasound-confirmed fatty livers were randomized to 3 g/d EPA+DHA or an olive oil placebo and took daily capsules for 24 weeks. Serum samples were taken at baseline, and 24 weeks. Samples from 120 subjects were analysed using UHPLC-MS for 233 lipid metabolites (OWL, Spain). Differences were statistically determined using the paired or unpaired (dependent on the data type) students t-test on log2 change. Results: Significant changes in numerous bioactive lipid metabolites was seen in the O3FA intervention group compared to placebo, particularly in the glycerophospholipids PE, LPE, PC, and LPC. An overall decrease in diglycerides and triglycerides with shorter chain fatty acids was seen whereas an increase was seen in triglycerides with increased fatty acid chain length and double bond number, reflecting EPA and DHA incorporation into these molecules. Some ceramide and sphingolipid species were also significantly decreased in the O3FA group. Conclusion: O3FA supplementation has previously been shown to increase the omega-3 index in NAFLD patients and to have beneficial effects at daily doses at or above 3 g EPA+DHA. Here we show that bioactive lipid species often associated with poor prognosis (diglycerides, ceramides and sphingolipids) are decreased, and beneficial lipid species in particular, PE, LPE, PC and LPC are increased after O3FA intervention. Of particular interest is the change in the bioactive lipids such as LPCs, which may facilitate omega-3 effects associated with NAFLD. O3FA significantly decreased the plasma triglyceride concentration as expected; this lipidomic analysis demonstrated that O3FA significantly shifts the trigflyceride species profile with longer fatty acyl-chain and greater unsaturation.

• Publisher: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: Fatty acids / Fatty liver / Gastroenterology / Lipids / Metabolites / Omega-3 fatty acids / Triglycerides