Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses

Abstract

Rationale: Specialized pro-resolving mediators (SPM—lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. Objective: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. Methods and Results: Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo. Conclusions: Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT03347006.

Resolvin E1 derived from eicosapentaenoic acid prevents hyperinsulinemia and hyperglycemia in a host genetic manner

“…EPA driving an upregulation in the concentration of RvE1's precursor is highly consistent with a recent clinical trial to show that consumption of an n-3 PUFA supplement promoted a strong upregulation of SPMs within 24 hours. 44 A major advancement is that our data show RvE1 could improve hyperinsulinemia and hyperglycemia via ERV1/ ChemR23. RvE1 treatment is likely exerting its effects through multiple mechanisms.…”

Obesity-Driven Deficiencies of Specialized Pro-resolving Mediators May Drive Adverse Outcomes During SARS-CoV-2 Infection

“…It is important to note that over-the-counter formulations of these fatty acids are not the same as prescriptions due to differences in dose, purity, and composition of the fatty acids. Nevertheless, a recent study showed that an SPM precursor containing marine oil strongly upregulated SPMs of the EPA and DHA series within hours of administration accompanied by enhanced neutrophil and monocyte phagocytosis of bacteria (62). However, a major limitation of this approach is that dietary EPA and DHA may not be as potent as direct intervention with SPMs (12).…”

Higher omega-3 index after dietary inclusion of omega-3 phospholipids versus omega-3 triglycerides in Alaskan Huskies

“…Another interesting focus area for a potential follow-up study could be the specialized ­pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) that are produced by enzymatic conversion of essential FAs, including omega-3 PUFAs. Inasmuch, DHA- and EPA-derived SPMs may help in the reduction of vascular and systemic inflammation [ 28 ]. Hence, increasing dietary omega-3 intake may have wide health benefits that are not limited to omega-3 PUFAs directly [ 1 ].…”