Human lipoxygenase isoforms form complex patterns of double and triple oxygenated compounds from eicosapentaenoic acid

Omega‐3 fatty acids protect from colitis via an Alox15‐derived eicosanoid

“…To explore the underlying mechanism, we finally performed 15S‐HEPE supplementation studies (Figures 4,5). 15‐HEPE is the major product of mouse Alox15 catalyzed the oxygenation of EPA 32 . EPA is present at elevated concentrations in fat1 mice (Table 1) and we detected this metabolite at relatively high concentrations in inflamed colon specimens of TNBS‐treated (Figure 2H) and DSS‐treated (Figure 3H) mice.…”

“…Significant differences (*P < .05, **P < .01 by Mann-Whitney U Test) are indicated and for borderline significances, the P values are given Alox15 catalyzed the oxygenation of EPA. 32 EPA is present at elevated concentrations in fat1 mice (Table 1) and we detected this metabolite at relatively high concentrations in inflamed colon specimens of TNBS-treated (Figure 2H) and DSS-treated (Figure 3H) mice. When we pre-treated wildtype mice with 15S-HEPE and subsequently challenged the animals with TNBS (Figure 4) or DSS (Figure 5) we found that the intensity of inflammatory symptoms was strongly reduced.…”

“…Alox15 catalyzed the oxygenation of EPA. 32 EPA is present at elevated concentrations in fat1 mice (Table 1) and we detected this metabolite at relatively high concentrations in inflamed colon specimens of TNBS-treated ( Figure 2H) and DSS-treated ( Figure 3H) mice. When we pre-treated wildtype mice with 15S-HEPE and subsequently challenged the…”

“…Fat1 mice have increased EPA concentrations (Table 1) and this n-3 PUFA is converted by mouse Alox15 to 15-HEPE. 32 Furthermore, fat1 overexpression protected mice from TNBS-and DSS-induced colitis and systemic expression silencing of Alox15 abolished this protective effect (Figures 2 and 3). Taken together, these data suggest that the protective effect of fat1 overexpression may be related to the Alox15-dependent in vivo formation of 15-HEPE.…”

E-series resolvin metabolome, biosynthesis and critical role of stereochemistry of specialized pro-resolving mediators (SPMs) in inflammation-resolution: Preparing SPMs for long COVID-19, human clinical trials, and targeted precision nutrition

“…The proposed biosynthesis of RvE4 was recently independently confirmed with purified recombinant human enzymes using 5-lipoxygenase (5-LOX) and 15-LOX with substrate EPA in vitro [ 86 ]. We establish the complete stereochemistry of RvE4 and its potent functions with isolated human macrophage-mediated efferocytosis employing results from detailed matching experiments [ 61 ].…”