Abomasal infusion of docosahexaenoic acid elevates circulating anti-inflammatory, pro-resolving oxylipins in dairy cows

Supplementation of lactating dairy cows with n-3 fatty acids (FA) has been shown to modulate inflammatory responses and improve reproductive function. Among the n-3 FA used in dairy diets, docosahexaenoic acid (DHA; C22:6n-3) is a substrate for the biosynthesis of oxylipins (OXL) with pro-resolving and anti-inflammatory functions. These OXL represent a well-documented mechanism by which n-3 supplementation modulates inflammatory responses. However, the magnitude of this response when known amounts of DHA are delivered postruminally remains unknown. Our study's objective was to evaluate the effects of DHA supplementation on the plasma OXL profile in lactating dairy cows. Eight ruminally cannulated multiparous cows (97 ± 37 DIM, 49 ± 3 kg milk/d) were assigned to a 4 × 4 Latin square treatment sequence with 21-d periods consisting of 10 d of washout and 11 d of infusion. Docosahexaenoic acid derived from enriched algal oil (65% DHA) was suspended in ethanol (∼200 g/d) and infused abomasally at 0, 2, 4, or 6 g/d for 11 d. Plasma samples were collected via coccygeal venipuncture on d 11 of each period for targeted lipidomic analysis using HPLC tandem MS. Abomasal infusion of DHA increased plasma concentrations of DHA-derived oxylipins 4-, 14-, and 20-hydroxydocoasahexaenoic acid (HDoHE) and tended to enhance 10-HDoHE in a linear, dose-dependent manner. In contrast, DHA supplementation was inversely correlated with plasma concentrations of the proinflammatory, arachidonic acid-based oxylipins 5S,15S-dihydroxy-eicosatetraenoic acid and 8,9-dihydroxyeicosatrienoic acid. Our results demonstrate that abomasal infusion of DHA increases concentrations of DHA-derived anti-inflammatory and pro-resolving oxylipin species, including HDoHE, which may limit excessive lipolysis and inflammation in dairy cows.