Plasma non-esterified FA and oxylipids were isolated from 123 Caucasian males using solid phase extraction and quantified using high performance liquid chromatography-tandem mass spectrometry. Statistical analyses included linear regressions and polytomous logistic regressions, and the responses were body mass index (BMI) and waist circumference (WC), and serum
leptin, total
adiponectin,
interleukin-6 (IL-6),
tumor necrosis factor-α (TNF-α), and
C-peptide. Models were adjusted for age and smoking, and p-values were corrected for false discovery per Benjamini-Hochberg and Bonferroni.
RESULTS: We report that BMI, WC, and several serum
cytokines were highly associated
arachidonic acid (ARA)-derived
hydroxyeicosatetraenoic acids (HETEs), and vicinal diols (i.e.,
alcohols on adjacent
carbon atoms) derived from several PUFAs. There was a significant linear relationship between BMI, WC, and serum
leptin, and ARA-derived 5-, 11-, and
15-HETE. Specifically, BMI and WC were positively associated with proinflammatory 5- and 11-hydroxyeicosatetraenoic
acid (
HETE), even after normalization to ARA concentrations and false discovery p-value correction. Individuals with
5-HETE concentrations >5.01nmol/L or
11-HETE concentrations and >0.89nmol/L were over 5 times more likely to be obese compared to those with ≤1.86nmol/L and ≤0.39nmol/L, respectively. Vicinal diols from linoleic, eicosapentaenoic, and
docosahexaenoic acid were inversely associated with
obesity. Across all statistical tests, vicinal diols were inversely associated with
obesity whether normalized to parent PUFA concentrations or normalized to precursor
epoxides. Interestingly, the proinflammatory
cytokines IL-6 and TNF-α were not associated with any oxylipids. Since
5-HETE is a 5LOX product,
11-HETE is marker of lipid peroxidation, and vicinal diols are formed through soluble
epoxide hydrolase (sEH) metabolism of CYP epoxygenated PUFAs, therefore, these results indicate that
obesity is likely associated with altered metabolism with distinct oxygenating pathways. Taken together, our results indicate that
obesity is associated with specific oxylipids indicative of altered PUFA metabolism through several pathways (i.e., LOX,
reactive oxygen species, and sEH and CYP epoxygenase), rather than attributed solely to altered dietary PUFA intake.