Abstract #M276

# M276
A lipidomic analysis of bovine liver during metabolic disease.
Sina Saed Samii1,2, Yu Zang2, William A. Myers*1,2, Ester Grilli3, Joseph W. McFadden1,2, 1Cornell University, Ithaca, NY, 2West Virginia University, Morgantown, WV, 3University of Bologna, Bologna, Italy.

Steatosis develops with elevations in hepatic free fatty acid (FFA) uptake, triacylglycerol (TAG) esterification, and ketogenesis. We previously performed a plasma lipidomic analysis of peripartal dairy cows to reveal postpartum (pp) decreases in plasma phosphatidylcholines (PC; e.g., PC 32:3) as a feature of fatty liver, hyperlipidemia, and ketosis. Our objective was to identify specific hepatic lipids that are related to steatosis, lipolysis, and ketone production using lipidomics. Thirty multiparous Holstein cows were enrolled −28 d prepartum and fed diets formulated to meet or exceed requirements. Blood and liver samples were routinely collected. Untargeted lipidomics was performed using mass spectrometry. Univariate and multivariate analyses of auto-scaled lipidomic data were performed. Cows were separately categorized into low or high FFA area under the curve (FFAAUC; d 1 – 14 pp; 4,915 ± 1,369 vs. 12,501 ± 2,761 [μmol/L × 14 d]; n = 18), β-hydroxybutyrate area under the curve (BHBAUC; d 1 – 14 pp; 4,583 ± 459 vs. 7901 ± 1,206 [μmol/L × 14 d]; n = 18), or mean pp liver lipid content (d 5 and 14 pp; 5 ± 1 vs. 12 ± 2% of wet weight; n = 18). Lipidomics revealed 403 lipids. Random forest analysis determined that cows were distinguishable across time (class error = 0.10). PLS-DA score plots demonstrated good fitness and high predictability of model with R2 and Q2 values ≥0.75 and 0.74, respectively. Postpartum increases in monoalkyl-diacylglycerols (MADAG; e.g., 58:2; P < 0.05) were observed. In contrast, pp changes in hepatic phosphatidylethanolamine (PE) levels were inconsistent (e.g., PE 42:4 increased, whereas PE 38:2 decreased; P < 0.05). Interestingly, hepatic TAG saturation increased while PC saturation decreased as steatosis progressed (P < 0.05). Cows with high liver lipid experienced elevations in hepatic TAG 56:9 and 54:1 as well as phosphatidylserine (PS) 39:3 (P < 0.05). Cows with lower FFAAUC had higher levels of PE 35:0 and phosphatidic acid (PA) 39:1 (P < 0.05). Cows with high BHBAUC had greater postpartum levels of hepatic MADAG 64:4, PA 45:2, and PS 46:2 (P < 0.05). We conclude that dynamic remodeling of the bovine liver is related to metabolic disease.

Key Words: lipidome, peripartum, steatosis