Liver transcriptome profiles of dairy cows with different serum metabotypes

In a previously established animal model, 38 multiparous Holstein cows were assigned to 2 groups fed different diets to achieve either a normal (NBCS) or high (HBCS) body condition score (BCS) and backfat thickness (BFT) until dry-off at −49 d before calving (NBCS: BCS 1.4 cm [2.36 ± 0.35], mean ± SD). The groups were also stratified for comparable milk yields (NBCS: 10,361 ± 302 kg; HBCS: 10,315 ± 437 kg; mean ± SD). The cows were then fed the same diet during the dry period and subsequent lactation, maintaining the differences in BFT and BCS throughout the study. Using the serum metabolomics data, we created a classification model that identified different metabotypes. Machine learning classifiers revealed a distinct cluster labeled HBCS-PN (HBCS predicted normal BCS) among over-conditioned cows. These cows showed higher feed intake and better energy balance than the HBCS-PH (high BCS predicted high BCS) group, while milk yield was similar. The aim of this study was to investigate the changes in the hepatic transcriptome of cows differing in serum-metabotype postpartum. We performed hepatic transcriptome analysis in cows from 3 metabolic clusters: HBCS-PH (n = 8), HBCS-PN (n = 6), and normal BCS predicted normal BCS (NBCS-PN, n = 8) on d 21 (±2) postpartum. Liver tissue from cows expressed a total of 13,118 genes aligned with the bovine genome. A total of 48 differentially expressed genes (DEG; false discovery rate ≤0.1 and fold-change >1.5) were found between NBCS-PN and HBCS-PH cows, whereas 24 DEG (14 downregulated and 10 upregulated) were found between HBCS-PN and HBCS-PH cows. The downregulated DEG (n = 31) in NBCS-PN cows compared with HBCS-PH cows are involved in biosynthetic processes such as lipid, lipoprotein, and cholesterol synthesis (e.g., APOA1, MKX, RPL3L, CANT1, CHPF, FUT1, ZNF696), cell organization, biogenesis, and localization (e.g., SLC12A8, APOA1, BRME1, RPL3L, STAG3, FBXW5, TMEM120A, SLC16A5, FGF21), catabolic processes (e.g., BREH1, MIOX, APOBEC2, FBXW5, NUDT16), and response to external stimuli (e.g., APOA1, FGF21, TMEM120A, FNDC4), whereas upregulated DEG (n = 17) are related to signal transduction and cell motility (e.g., RASSF2, ASPN, SGK1, KIF7, ZEB2, MAOA, ACKR4, TCAF1), suggesting altered metabolic adaptations during lactation. Our results showed 24 DEG between HBCS-PN and HBCS-PH in the liver. The expression of SLC12A8, SLC16A5, FBXW5,