The expression of genes involved in hepatic metabolism is altered by temporary changes to milking frequency

Changes to milking frequency (MF) affect the metabolic and energetic status of dairy cows. However, the duration of altered MF necessary to modify hepatic transcription during early lactation is less clear. Additionally, long-term responses to short-term alterations in MF have not been established. Holstein-Friesian dairy cows (n = 120) were allocated to 3 or 6 wk of either once-daily (1 ×) or thrice-daily (3 ×) milking, immediately postpartum. Following treatment, cows were switched to twice-daily (2 ×) milking. These 4 treatment groups were compared with cows milked 2 × (n = 30) for the whole lactation. Liver tissue was collected by biopsy at 1, 3, 6, and 9 wk postpartum from 12 cows per treatment, RNA was extracted, and transcript abundance of genes involved in hepatic metabolism was quantified. Milking frequency altered the expression of most of the genes measured; however, we observed no effects caused by the length of time on the alternative milking frequency and no interactions between MF and length. During the MF treatment, mRNA expression of some, but not all, genes involved in gluconeogenesis (G6PC, PCK1), fatty acid β-oxidation (CPT1A, CPT2), ketogenesis (HMGCS2), lipid transport (APOA1), and lipolysis (PNPLA2) were lower for cows milked 1 × and plasma glucose and insulin concentrations were greater. Cows milked 3 × had reduced mRNA expression for some of the genes involved in fatty acid synthesis (ACACA) and lipid transport (APOB) and had greater plasma NEFA concentrations at wk 1. At 9 wk postpartum, expression data indicated that cows previously milked 3 × had a greater capacity for gluconeogenesis (PCK1), ketogenesis (HMGCS2), and urea cycling (ASL, CPS1) and lower glucose concentrations than cows previously milked 1 ×, because some of the genes involved in these processes were still altered. Milking cows 1 × relative to 2 ×, however, did not result in significant carryover effects on the expression of the genes measured in this study, indicating that metabolic changes are not sustained beyond the period of reduced MF. Changes to MF altered the hepatic response during early lactation; however, this was not dependent on the duration of MF change. Although we observed only minimal carryover effects on hepatic metabolism from short periods of reduced MF postpartum, there may be long-term effects on urea cycling (ASL, CPS1) and ketogenesis (HMGCS2) when 3 × milking occurs immediately postpartum.