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Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

ABSTRACT: The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA-rich fish oil supplementation increased SPM precursor 17-hydroxy docosahexaenoic acid (17-HDHA) concentrations in maternal and umbilical cord blood (P = 0.02). We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P = 0.049). Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P < 0.001, both).

SUBMITTER: Mozurkewich EL

PROVIDER: S-EPMC5013256 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

Mozurkewich Ellen L EL Greenwood Matthew M Clinton Chelsea C Berman Deborah D Romero Vivian V Djuric Zora Z Qualls Clifford C Gronert Karsten K

Frontiers in pharmacology 20160907

The omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are precursors to immune regulatory and specialized pro-resolving mediators (SPM) of inflammation termed resolvins, maresins, and protectins. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX) and 15-LOX metabolic pathway precursors and downstream metabolites. We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and M ...[more]

PMID: 27656142

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Project description:BACKGROUND:We sought to determine whether prenatal supplementation with the omega-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) would increase markers of insulin sensitivity in maternal or cord blood compared with placebo supplementation. A secondary aim was to evaluate the association of serum EPA and DHA fractions with adiponectin, leptin and the adiponectin:leptin ratio (ALR). We hypothesized that omega-3 fatty acid supplementation would increase markers of insulin sensitivity in maternal and umbilical cord plasma. METHODS:We analyzed stored plasma samples collected from a prior 3-arm prospective, double-blinded, randomized controlled trial in which 126 women with singleton pregnancies between 12- and 20-weeks' gestation were randomized to receive: 1) an EPA-rich fish oil supplement, 2) a DHA-rich fish oil supplement, or 3) a soy oil placebo. Maternal venous blood samples were collected at 12-20?weeks gestation (before supplementation) and at 34-36?weeks gestation. At delivery, cord blood was collected. Samples were analyzed using sandwich enzyme-linked immunosorbent assay kits to quantify leptin and adiponectin levels which were utilized to calculate the ALR, a proxy measure for insulin sensitivity. RESULTS:We found no difference in adiponectin, leptin, and the ALR between the treatment and placebo groups at baseline, after supplementation, or in umbilical cord blood. In regression analyses, higher maternal serum DHA fraction was associated with increased ALR before (p?=?0.01) and after (p?=?0.04) DHA supplementation. There was no association of EPA fraction with any measure of insulin sensitivity. Cord blood DHA fraction was significantly associated with cord plasma leptin (p?=?0.02). Early pregnancy BMI was significantly associated with maternal leptin levels at baseline and in late pregnancy (p?<?0.001) and was inversely associated with the ALR (p?<?0.001). The ALR decreased significantly between the early and late pregnancy visits (p?<?0.001). Pregnancy weight gain was inversely associated with the ALR (P. <?0.02). CONCLUSIONS:EPA- and DHA- rich fish oil supplementation had no effect on plasma markers of insulin sensitivity. However, maternal serum DHA fraction was significantly associated with markers of insulin sensitivity. TRIAL REGISTRATION:https://clinicaltrials.gov/, registration number NCT00711971, 7/7/2008.

Project description:BACKGROUND:N-3 polyunsaturated fatty acid (PUFA) supplementation has been associated with reduced mortality and inflammation in patients with cardiovascular disease. There are limited data on the effects of n-3 PUFA supplementation in patients with peripheral artery disease (PAD). MATERIALS AND METHODS:The OMEGA-PAD II trial was a double-blinded, randomized, placebo-controlled trial to assess the effect of 3 mo of high-dose oral n-3 PUFA supplementation on inflammation, endothelial function, and walking ability in patients with PAD. RESULTS:Twenty-four patients with claudication received 4.4 g/d of fish oil or placebo for 3 mo. Outcomes measured included high-sensitivity C-reactive protein levels, the omega-3 index, endothelial function as measured via flow-mediated vasodilation, walking impairment questionnaire, and a 6-min walk test. Plasma levels of specialized pro-resolving lipid mediators (SPMs) were measured by liquid-chromatography-tandem mass spectrometry. In patients treated with fish oil, the absolute mean omega-3 index significantly increased from baseline (fish oil: 7.2 ± 1.2%, P < 0.001; placebo: -0.4 ± 0.9%, P = 0.31; between-group P < 0.001). Furthermore, there were significant increases in several pathway markers of SPM biosynthesis, including several mono-hydroxyeicosapentaenoic acids and mono-hydroxydocosahexaenoic acids. We also observed significant increases in the SPM lipoxin A5 (fish oil: 0.57 ± 0.70 pg/mL, P = 0.05; placebo: 0.01 ± 0.38 pg/mL, P = 0.93; between-group P = 0.04) and resolvin E3 (fish oil: 154 ± 171 pg/mL, P = 0.04; placebo: 32 ± 54 pg/mL, P = 0.08; between-group P = 0.04). There were no significant changes in high-sensitivity C-reactive protein, flow-mediated vasodilation, walking impairment questionnaire, or 6-min walk test in the fish oil group. CONCLUSIONS:Fish oil increases SPMs in plasma of patients with PAD. Further studies are required to determine whether these early changes translate to clinical improvements in patients with PAD.

Dataset Information

Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

Publications

Pathway Markers for Pro-resolving Lipid Mediators in Maternal and Umbilical Cord Blood: A Secondary Analysis of the Mothers, Omega-3, and Mental Health Study.

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