Omega-3 to omega-6 fatty acid oxidation ratio as a novel inflammation resolution marker for metabolic complications in obesity

Nutr Metab Cardiovasc Dis. 2023 Jun;33(6):1206-1213. doi: 10.1016/j.numecd.2023.03.007. Epub 2023 Mar 21.

Abstract

Background and aims: The oxidative metabolism of polyunsaturated fatty acids (PUFAs) leads to bioactive isoprostanoids. The aim was to establish the associations of a complete urinary isoprostanoid profiling in a cohort study of carefully phenotyped obese subjects to determine possible potential differential implications for omega-6 PUFA- and omega-3 PUFA-derived isoprostanoids for obesity, metabolic indicators, and inflammation.

Methods and results: PUFA peroxidation compounds were determined in urine samples from obese human subjects (n = 46) by liquid chromatography coupled to tandem mass spectrometry. Increased omega-6 arachidonic acid (AA) oxidation, mainly represented by 5-F2c isoprostane (5-F2c-IsoP) and metabolites of 15-F2t-IsoP, was associated with body mass index, glycated hemoglobin (HbA1c) and mean arterial blood pressure. In addition, we identified the omega-3 PUFA-derived urinary metabolites 14-F4t-NeuroP from docosahexaenoic acid (DHA) and 5-F3t-IsoP from eicosapentaenoic acid (EPA), which declined with age. The omega-3 to omega-6 oxidation ratio was a significant predictor of inflammation in obesity.

Conclusion: The findings point to full urinary isoprostanoid profiling as a more sensitive measure of PUFA oxidative stress in obesity-induced metabolic complications compared with individual isoprostanoid measures. Furthermore, the results suggest the balance between the omega-3 and omega-6 PUFA oxidation as determinative for the consequences of oxidative stress on inflammation in obesity.

Keywords: Cardiovascular risk; Diabetes; Inflammation; Isoprostanes; Lipid mediators; Obesity; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Fatty Acids, Omega-3*
  • Fatty Acids, Omega-6*
  • Fatty Acids, Unsaturated
  • Humans
  • Inflammation / diagnosis
  • Obesity / diagnosis

Substances

  • Fatty Acids, Omega-6
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated