Effect of omega-3 ethyl esters on the triglyceride-rich lipoprotein response to endotoxin challenge in healthy young men

Rachel E. Walker, Chesney K. Richter, Ann C. Skulas-Ray, Michael R. Flock, Brian A. Harsch, Carmen E. Annevelink, Penny M. Kris-Etherton, Gordon L. Jensen, Gregory C. Shearer

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Oxylipins are produced enzymatically from polyunsaturated fatty acids, are abundant in triglyceride-rich lipoproteins (TGRLs), and mediate inflammatory processes. Inflammation elevates TGRL concentrations, but it is unknown if the fatty acid and oxylipin compositions change. In this study, we investigated the effect of prescription ω-3 acid ethyl esters (P-OM3; 3.4 g/d EPA þ DHA) on the lipid response to an endotoxin challenge (lipopolysaccharide; 0.6 ng/kg body weight). Healthy young men (N = 17) were assigned 8-12 weeks of P-OM3 and olive oil control in a randomized order crossover study. Following each treatment period, subjects received endotoxin challenge, and the time-dependent TGRL composition was observed. Postchallenge, arachidonic acid was 16% [95% CI: 4%, 28%] lower than baseline at 8 h with control. P-OM3 increased TGRL ω-3 fatty acids (EPA 24% [15%, 34%]; DHA 14% [5%, 24%]). The timing of ω-6 oxylipin responses differed by class; arachidonic acid-derived alcohols peaked at 2 h, while linoleic acid-derived alcohols peaked at 4 h (pint = 0.006). P-OM3 increased EPA alcohols by 161% [68%, 305%] and DHA epoxides by 178% [47%, 427%] at 4 h compared to control. In conclusion, this study shows that TGRL fatty acid and oxylipin composition changes following endotoxin challenge. P-OM3 alters the TGRL response to endotoxin challenge by increasing availability of ω-3 oxylipins for resolution of the inflammatory response.

Original languageEnglish (US)
Article number100353
JournalJournal of Lipid Research
Issue number5
StatePublished - May 2023


  • VLDL
  • chylomicrons
  • fatty acids
  • inflammation
  • lipopolysaccharide
  • lipoprotein kinetics
  • omega-3 acid ethyl esters
  • oxylipins
  • polyunsaturated fatty acids
  • triglycerides

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology


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