Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity

Abstract

Background: Specialized pro-resolving mediators (SPMs), synthesized from PUFAs, resolve inflammation and return damaged tissue to homeostasis. Thus, increasing metabolites of the SPM biosynthetic pathway may have potential health benefits for select clinical populations, such as subjects with obesity who display dysregulation of SPM metabolism. However, the concentrations of SPMs and their metabolic intermediates in humans with obesity remains unclear.

Objectives: The primary objective of this study was to determine if a marine oil supplement increased specific metabolites of the SPM biosynthetic pathway in adults with obesity. The second objective was to determine if the supplement changed the relative abundance of key immune cell populations. Finally, given the critical role of antibodies in inflammation, we determined if ex vivo CD19 + B-cell antibody production was modified by marine oil intervention.

Methods: Twenty-three subjects [median age: 56 y; BMI (in kg/m2): 33.1] consumed 2 g/d of a marine oil supplement for 28-30 d. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic (HEPE), 14-hydroxydocosahexaenoic acid (14-HDHA), and 17-HDHA. Blood was collected pre- and postsupplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B-cell isolation. Paired t-tests and Wilcoxon tests were used for statistical analyses.

Results: Relative to preintervention, the supplement increased 6 different HEPEs and HDHAs accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 concentrations were increased 3.5- and 4.7-fold upon intervention, respectively. The supplement did not increase the concentration of D-series resolvins and had no effect on the abundance of immune cells. Ex vivo B-cell IgG but not IgM concentrations were lowered postsupplementation.

Conclusions: A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased concentrations of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov as NCT04701138.

Keywords: antibody; inflammation; obesity; omega-3; polyunsaturated fatty acids; specialized pro-resolving mediators.

© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.

Figures

FIGURE 1

Marine oil supplement increases EPA-, DPA- and DHA-derived metabolites in adults with obesity. EPA-derived metabolites: RvE1 (A), 11-HEPE (B), 15S-HEPE (C), and 5-HEPE (D). DPA-derived: MaR1-n3-DPA (E). DHA-derived metabolites: 7-HDHA (F), 13-HDHA (G), and 17-HDHA (H); n = 23 for all metabolites. P values and BH-adjusted P values are denoted underneath the header of each metabolite. Dots represent individual pre- and postsupplementation values, and the box plot represents median and IQR limits. DHA, docosahexaenoic acid; DPA; docosapentaenoic acid; HDHA, hydroxydocosahexaenoic acid; HEPE, hydroxyeicosapentaenoic acid; MaR1, maresin 1; SPM, specialized pro-resolving mediator.

FIGURE 2

Marine oil supplement differentially influences AA-derived metabolites in adults with obesity. AA-derived metabolites: 11-HETE (A), 15-HETE (B), 12-HETE (C), 12S-HHTrE (D), TXB2 (E), PGF2α (F), and LTB4 (G); n = 23 for all metabolites. P values and BH-adjusted P values are denoted underneath the header of each metabolite. Dots represent individual pre- and postsupplementation values, and the box plot represents median and IQR limits. AA, arachidonic acid; HETE, hydroxyeicosatetraenoic acid; LTB4, leukotriene B4; PGF2α, prostaglandin F2α; SPM, specialized pro-resolving mediator; TXB2, thromboxane B2; 12S-HHTrE, 12S-hydroxy-5Z,8E,10E-heptadecatrienoic acid.

FIGURE 3

Marine oil supplement increases the concentration of EPA and DHA while lowering AA in adults with obesity. Plasma concentration of 14:0 (A), 16:0 (B), 20:4(n-6) (C), 20:5(n-3) (D), 22:4(n-6) (E), and 22:6(n-3) (F); n = 23 for all fatty acids. P values and BH-adjusted P values are denoted for each fatty acid. Dots represent individual pre- and postsupplementation values, and the box plot represents median and IQR limits. AA, arachidonic acid; DHA, docosahexaenoic acid; SPM, specialized pro-resolving mediator.

FIGURE 4

Ex vivo IgG but not IgM concentrations are decreased postsupplementation with a marine oil supplement in adults with obesity. Unstimulated (A) and stimulated B-cell IgM production (B). Unstimulated (C) and stimulated (D) B-cell IgG production. P value is denoted by *** < 0.005. Bar plots are presented as mean ± SEM; n = 22.