Identification of inflammatory and proresolving lipid mediators in bone marrow and their lipidomic profiles with ovariectomy and omega-3 intake.

Newly described lipoxygenase (LOX)-generated lipid mediators, that is, resolvins and protectins as well as lipoxins, are both anti-inflammatory and proresolving. We aimed to determine whether these lipid mediators are present in bone marrow and whether their lipidomic profiles are altered following ovariectomy or dietary supplementation with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) ethyl esters. Female rats were ovariectomised or sham-operated. Shams and one ovariectomised group received a diet devoid of omega-3 long-chain polyunsaturated fatty acids. The remaining ovariectomised rats received either 0.5 g EPA or DHA ethyl ester/kg body weight/day for 4 months. Bone marrow was analyzed using both GC to determine fatty acid composition and mediator lipidomics by LC/MS/MS profiling for the presence of LOX-pathway lipid mediators derived from arachidonic acid (AA), EPA, and DHA. LOX-derived products including lipoxins, resolvin D1, resolvin E1, and protectin D1 were identified in bone marrow by the presence of diagnostic ions in their corresponding MS-MS spectra. The proportion of AA relative to DHA and of AA-derived relative to DHA-derived mediators in bone marrow was higher in ovariectomised compared to sham-operated rats. DHA or EPA ethyl ester supplementation increased the percentage of DHA and EPA in bone marrow and increased the proportion of LOX mediators biosynthesized from DHA or EPA, respectively. Given the potent bioactivities of the lipoxins, resolvins, and protectins, the presence and changes in profile postovariectomy and with EPA and DHA ethyl ester supplementation may be of interest in bone marrow function and as a potential source of these mediators in vivo