Omega‐6 and omega‐3 oxylipins as potential markers of cardiometabolic risk in young adults

Abstract

Objective Omega‐6 and omega‐3 oxylipins are known to play a role in inflammation and cardiometabolic diseases in preclinical models. The associations between plasma levels of omega‐6 and omega‐3 polyunsaturated fatty acid–derived oxylipins and body composition and cardiometabolic risk factors in young adults were assessed. Methods Body composition, brown adipose tissue, traditional serum cardiometabolic risk factors, inflammatory markers, and a panel of 83 oxylipins were analyzed in 133 young adults (age 22.1[SD 2.2] years, 67% women). Results Plasma levels of four omega‐6 oxylipins (15‐HeTrE, 5‐HETE, 14,15‐EpETrE, and the oxidative stress–derived 8,12‐iso‐iPF2α‐VI) correlated positively with adiposity, prevalence of metabolic syndrome, fatty liver index, and homeostatic model assessment of insulin resistance index and lipid parameters. By contrast, the plasma levels of three omega‐3 oxylipins (14,15‐DiHETE, 17,18‐DiHETE, and 19,20‐DiHDPA) were negatively correlated with adiposity, prevalence of metabolic syndrome, fatty liver index, homeostatic model assessment of insulin resistance index, and lipid parameters. The panel of seven oxylipins predicted adiposity better than traditional inflammatory markers such as interferon gamma or tumor necrosis factor‐alpha. Pathway analyses revealed that individuals with obesity had higher plasma levels of omega‐6 and lower plasma levels of omega‐3 oxylipins than normal‐weight individuals. Conclusion Plasma levels of seven omega‐6 and omega‐3 oxylipins may have utility as early markers of cardiometabolic risk in young adults.

Influence of Dietary Inulin on Fecal Microbiota, Cardiometabolic Risk Factors, Eicosanoids, and Oxidative Stress in Rats Fed a High-Fat Diet

“…Consumption of inulin also tended to decrease the amount of HETEs produced by LOX. In line with our findings, amounts of 15-HETrE, 5-HETE, 12-HETE and 15-HETE in plasma are increased in obesity conditions in humans [ 72 , 73 ]. PGE 2 derived from arachidonic acid via COX enzyme was the only selected and detected eicosanoid that tended to increase after receiving inulin.…”

“…Although PGE 2 is considered a pro-inflammatory lipid mediator, it can exhibit anti-inflammatory properties by reducing the production of cytokine tumor necrosis factor α, inhibiting 5-LOX enzyme involved in producing pro-inflammatory 4-series leukotrienes and 5-HETE, and enhancing 15-LOX enzyme involved in producing pro-resolving lipoxin A 4 [ 10 ]. In fact, plasma PGE 2 may be negatively correlated with parameters of adiposity, insulin resistance, and fatty liver in healthy young adults [ 72 ].…”

Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial

“…High omega-6 oxylipins and eCBs are indicators of higher pro-inflammatory status, high adiposity levels, cardiovascular disruption, liver dysfunction, and/or oxidative stress, 5 , 7 , 9 , 10 , 12 , 46 , 48 , 49 which concur with the findings observed in our cohort of young, sedentary adults. 50 Interestingly, we found that long-term exercise training, was an effective therapy to decrease the plasma levels of these metabolites. Acute exercise has been demonstrated to induce higher analgesic effects through increased eCBs levels.…”

Plasma Levels of Omega-3 and Omega-6 Derived Oxylipins Are Associated with Fecal Microbiota Composition in Young Adults

“…All blood samples were immediately centrifuged to obtain plasma aliquots (obtained with Vacutainer ® Hemogard™ tubes, containing the potassium salt of ethylenediaminetetraacetic acid as an anticoagulant) and stored at −80 °C. Plasma levels of omega-3 and omega-6 oxylipins were measured with a targeted metabolomics approach using liquid chromatography-tandem mass spectrometry (LC-MS/MS), with a method validated according to the Food and Drug Administration (FDA) bioanalytical method validation guidelines [ 25 ].…”