Background Specialized pro-resolving mediators (SPM), synthesized from polyunsaturated fatty acids (PUFA), 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 those with obesity that display dysregulation of SPM metabolism. However, bioavailability of SPMs and their metabolic intermediates in humans with obesity remains unclear. Objectives The primary objective 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 of 56y and BMI of 33.1, consumed 2 g/d of a marine oil supplement for 28–30 days. The supplement was particularly enriched with 18-hydroxyeicosapentaenoic, 14-hydroxydocosahexaenoic, and 17-hydroxydocosahexaenoic acids. Blood was collected pre/post supplementation for plasma mass spectrometry oxylipin and fatty acid analyses, flow cytometry, and B cell isolation. Paired T-tests/Wilcoxon tests were used for statistical analyses. Results Relative to pre-intervention, the supplement increased six different hydroxyeicosapentaenoic and hydroxydocosahexaenoic acids accompanied by changes in plasma PUFAs. Resolvin E1 and docosapentaenoic acid-derived maresin 1 levels were respectively increased 3.5 and 4.7-fold upon intervention. 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 levels were lowered post-supplementation. Conclusions A marine oil supplement increased select SPMs and their metabolic intermediates in adults with obesity. Additional studies are needed to determine if increased levels of specific SPMs control the resolution of inflammation in humans with obesity. This trial was registered at clinicaltrials.gov (NCT04701138).
Resolvin E1 (RvE1), a specialized pro‐resolving mediator (SPM), improves glucose homeostasis in inbred mouse models of obesity. However, an impediment toward translation is that obesity is a highly heterogenous disease in which individuals will respond very differently to interventions such as RvE1. Thus, there is a need to study SPMs in the context of modeling the heterogeneity of obesity that is observed in humans. We investigated how RvE1 controls the concentration of key circulating metabolic biomarkers using diversity outbred (DO) mice, which mimic human heterogeneity. We first demonstrate that weights of DO mice can be classified into distinct distributions of fat mass (i.e., modeling differing classes of obesity) in response to a high‐fat diet and in the human population when examining body composition. Next, we show RvE1 administration based on body weight for four consecutive days after giving mice a high‐fat diet led to approximately half of the mice responding positively for serum total gastric inhibitory polypeptide (GIP), glucagon, insulin, glucose, leptin, and resistin. Interestingly, RvE1 improved hyperleptinemia most effectively in the lowest class of fat mass despite adjusting the dose of RvE1 with increasing adiposity. Furthermore, leptin levels after RvE1 treatment were the lowest in those mice that were also RvE1 positive responders for insulin and resistin. Collectively, these results suggest a therapeutic fat mass‐dependent window for RvE1, which should be considered in future clinical trials. Moreover, the data underscore the importance of studying SPMs with heterogenous mice as a step toward precision SPM administration in humans.
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