Differences in amino acid and fatty acid metabolism contribute to variability in dairy cattle feed efficiency

Understanding the biology underlying variation in feed efficiency is crucial for improving nutrient use efficiency at the tissue and molecular level in dairy cows. This study aimed to identify key differences in hepatic nutrient metabolism by analyzing protein-level alterations through proteomics and quantifying associated changes in circulating AA levels between cows with high or low residual feed intake (RFI). A total of 92 mid-lactation (119 ± 33 DIM) primiparous (n = 34) and multiparous (n = 58) Holstein cows were enrolled in 42-d studies in 2 cohort groups. At the end of the experimental period, RFI for each cow was calculated by statistical determination of the deviation of actual intake of a cow from the expected intake, based on the average of the cohort. Cows within RFI values in the top and bottom 15% from each cohort were deemed high-efficiency (HE; low RFI) and low-efficiency (LE; high RFI), respectively. Liver and blood samples from 12 low-RFI (-1.67 ± 0.35) and 12 high-RFI (1.66 ± 0.25) cows with matching parity and DIM were analyzed using multidimensional liquid chromatography (LC)-MS, whereas plasma AA concentrations were quantified using LC-MS. Among the 20 AA quantified in blood, branched-chain AA, aromatic AA, and EAA were lower in HE cows compared with LE cows, likely reflecting the lower-than-expected feed intake in these cows. However, plasma glycine concentration was higher in HE cows. A total of 2,309 proteins were identified, with differential abundance observed in 183 proteins. Compared with LE cows, the 77 upregulated proteins in the liver enriched 5 pathways: Fatty Acid Degradation, AA Biosynthesis, TCA Cycle, 2-Oxocarboxylic Acid Metabolism, and Retinol Metabolism. In contrast, the 108 downregulated proteins enriched 12 pathways regulating ketogenesis as well as protein and AA catabolism. Taken together, the differences in plasma AA profile and liver proteome indicate that postabsorptive metabolic adaptations in HE cows, including enhanced fatty acid oxidation and AA synthesis, enable reduced feed intake without compromising milk production. Future research should focus on organ-specific nutrient flux and enzymatic activity, particularly in the mammary gland, to further unravel the mechanisms underlying feed efficiency.