A large multisite lipidomic investigation of parity and aging in dairy cows.

Efforts to optimize the longevity of dairy cows are hindered by the increased risk of adverse health events, culling, or dying on farm with increased parity. Lipidomics provides a platform to help identify important biomarkers and biological pathways associated with increased parity and associated aging. A large multisite (15 pasture-based, 15 TMR farms) cross-sectional study collected plasma samples from nonlactating, late pregnant, dry cows (n = 696, ∼27 d prepartum) and peak milk cows (n = 796, ∼58 DIM) in a disproportionate stratified random sampling frame (parity: 0, 1, 2, >2 for dry cows; 1, 2, 3, >3 for peak milk cows). A total of 185 lipid species, comprising the lipids classes of phospholipids, sphingomyelins (SM) and triacylglycerols, were quantified in a targeted, liquid chromatography-MS approach. Dry and peak milk cohorts were analyzed separately throughout. Variation in lipid profiles were mostly attributed to farm of origin (36%-41% of variation), with feeding system explaining 13% to 21% and parity explaining 6% to 9%, according to ANOVA simultaneous component analysis modeling. Multiple linear regression and orthogonal partial least squares (O-PLS) investigated the association of the lipid profile with age (d), whereas discriminant analysis compared first parity with >3 parity cows in O-PLS discriminant analysis, random forest, and support vector machine models. Rankings of the most important lipid species for each model type were compared. Phospholipids with 40 carbon atoms and 6 double bond equivalents (40:6) were consistently decreased with increasing parity and age across both dry and peak milk cohorts. These lipids most likely contained stearate (18:0) and docosahexaenoic acid (DHA, C22:6n-3), an n-3 fatty acid. Additionally, phospholipids with 40:5 and 38:6, lysophosphatidylcholine (17:0), SM(35:1), and SM(35:2) were commonly identified lipids that decreased in concentration with parity and age. Docosahexaenoic acid has been associated with improved cattle health, reproduction, and milk production and quality. This study raises the hypothesis that reduced DHA levels in older cows may be an important factor increasing susceptibility to adverse health events, reduced reproductive performance, and herd removal. Studies that supplement DHA or its precursors can test this hypothesis and may be important in optimizing longevity of cows.