Improving dairy cow feed efficiency is critical to the sustainability and profitability of dairy production, yet the underlying mechanisms that contribute to individual cow variation in feed efficiency are not fully understood. The objectives of this study were to (1) identify genes and associated pathways that are altered in cows with high- or low-residual feed intake (RFI) using RNA sequencing, and (2) determine if rumen-protected choline supplementation during mid-lactation would influence performance or feed efficiency. Mid-lactation (134 +/- 20 days in milk) multiparous Holstein cows were randomly assigned to either supplementation of 0 g/d supplementation (CTL; n = 32) or 30 g/d of a rumen-protected choline product (RPC; 13.2 g choline ion; n = 32; Balchem Corp., New Hampton, NY, USA). Residual feed intake was determined as dry matter intake regressed on milk energy output, days in milk, body weight change, metabolic body weight, and dietary treatment. The 12 cows with the highest RFI (low feed efficient; LE) and 12 cows with the lowest RFI (high feed efficient; HE), balanced by dietary treatment, were selected for blood, liver, and muscle analysis. No differences in production or feed efficiency were detected with RPC supplementation, although albumin was greater and arachidonic acid tended to be greater in RPC cows. Concentrations of beta-hydroxybutyrate were greater in HE cows. Between HE and LE, 268 and 315 differentially expressed genes in liver and muscle tissue, respectively, were identified through RNA sequencing. Pathway analysis indicated differences in cell cycling, oxidative stress, and immunity in liver and differences in glucose and fatty acid pathways in muscle. The current work indicates that unique differences in liver and muscle post-absorptive nutrient metabolism contribute to sources of variation in feed efficiency and that differences in amino acid and fatty acid oxidation, cell cycling, and immune function should be further examined.
