Hepatic metabolomics and transcriptomics in prepartal dairy cows supplemented with Smartamine M and MetaSmart during the transition period
Supplementation with Smartamine M (SM) and MetaSmart (MS) during the transition period improves postpartal dry matter intake, milk production, and blood neutrophil immune function. In the current study we used metabolomics and transcriptomics to provide a more holistic view of the adaptations induced on the liver by dry period nutrition. Liver from cows fed a control high-energy diet without (OVE) or with SM or MS were used. Metabolomics was performed via LC-MS and GC-MS (Metabolon Inc.) and transcriptomics using a whole-transcriptome bovine microarray (Agilent). From a total of 313 biochemical compounds identified, metabolomics analysis (P ≤ 0.10) revealed a total of 20, 21, and 48 compounds affected by SM vs. OVE, MS vs. OVE, and SM vs. MS, respectively. Comparing profiles in SM vs. OVE revealed that compounds up-regulated belong to the pentose, sterol, inositol, and purine metabolism pathways, while down-regulated compounds belong to secondary bile acid, arginine and proline, purine and pyrimidine, and eicosanoid metabolism pathways. In MS vs. OVE, the compounds up-regulated belong to primary bile acid, pyrimidine, and lysolipid metabolism, while compounds down-regulated were linked with glycolysis, gluconeogenesis, urea cycle, sphingolipid, and pyruvate metabolism. Liver of MS vs. OVE cows had lower hydroxybutyrate and lactate concentration. The transcriptomic analysis of these groups resulted in 922 (SM vs. OVE), 1,573 (MS vs. OVE) and 1,033 (SM vs. MS) differentially expressed genes (DEG, P ≤0.05). Bioinformatics analysis using the Dynamic Impact Approach (DIA) that SM vs. OVE resulted in a marked impact and activation of ‘fatty acid biosynthesis’, ‘cyanoamino acid metabolism’, ‘O-glycan biosynthesis’, and ‘glycosaminoglycan biosynthesis’. In MS vs. OVE, however, among the top-5 most-impacted pathway there was marked inhibition of ‘phenylalanine, tyrosine, and tryptophan biosynthesis’ and ‘phenylalanine’ metabolism. ‘Cyanoamino acid metabolism’ and ‘taurine and hypotaurine’ metabolism were highly-impacted and activated pathways in MS vs. OVE. Unique responses in SM vs. MS included a marked activation of ‘fatty acid biosynthesis’, ‘glycosphingolipid metabolism’, ‘valine, leucine, and isoleucine biosynthesis’, and ‘sulfur metabolism’. Preliminary data interpretation suggests MS and SM induce distinct changes on the metabolome and transcriptome phenotype of the prepartal liver. The functional relevance of such changes remains to be determined.
Keywords: Systems Biology, Metabolic Profiling, Bovine Liver