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Effects of acute intravenous trimethylamine N-oxide infusion on the bovine lipidome and metabolome during early lactation.

W. A. Myers



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Effects of acute intravenous trimethylamine N-oxide infusion on the bovine lipidome and metabolome during early lactation.
F. Wang1,2, W. A. Myers*1, C. Chang1, A. N. Davis1, J. E. Rico1, B. N. Tate1, L. F. Wang1,3, J. W. McFadden1. 1Cornell University Ithaca, NY, 2China Agricultural University Beijing, China, 3Henan Agricultural University Zhengzhou, China.

Bacteria convert choline and carnitine to trimethylamine in the gastrointestinal tract. In the liver trimethylamine is converted to trimethylamine N-oxide (TMAO), which may contribute to metabolic disease in rodents. In an exploratory manner, our objective was to determine whether TMAO modulates metabolism in cows. Eight early lactation Holstein cows (30.4 � 6.41 DIM) were enrolled in a study with a 4 � 4 replicated Latin square design. Cows were intravenously infused TMAO at 0 (control), 20, 40, or 60 g/d for 6 d. Washout periods lasted 9 d. Blood, milk, and liver tissue were collected on d 6. Untargeted lipidomics (nonpolar hydrophobic lipids; plasma) and metabolomics (polar hydrophilic compounds; serum, milk, and liver) were performed using C30 and pHILIC columns on a mass spectrometry platform in positive and negative modes, respectively. Statistical analysis was performed using MetaboAnalyst 4.0 following generalized log-transformation and auto-scaling. Data were analyzed using ANOVA and partial least squares discriminant analysis (PLS-DA). Following summation within lipid chain length, lipidomics analysis revealed 143 plasma lipids. The PLS-DA model distinguished TMAO treatments; however, only 44 lipids (~31%) were modified by TMAO treatment. No apparent pattern behaviors were observed. Examples of changes were limited to phosphatidylcholines (e.g., PC 36:4 and 37:2 were lower and PC 37:5 was higher in cows infused 60 g of TMAO/d, relative to control; false discover rate <0.05). Metabolomics analyses revealed 52 serum, 12 milk, and 39 liver compounds with a mzCloud mass spectral score > 75%; however, detected metabolites exceeded 100 for each sample type. These included amino acids, creatine, carnitine, and choline. We were not able to distinguish treatment metabolomes with PLS-DA. In addition, ANOVA did not detect differences in any metabolites with TMAO treatment. We conclude that the acute intravenous infusion of TMAO does not modify the bovine metabolome. Muted changes in the plasma lipidome in response to TMAO also suggest that this metabolite does not overtly modify metabolism in cows.

Keywords: cow, metabolome, trimethylamine N-oxide.