Relationships between metabolic profiles and gene expression in liver and leukocytes of dairy cows in early lactation

D. C. Wathes, Z. Cheng, Mazdak Salavati, L. Buggiotti, H Takeda, L. Tang, F. Becker, K.I. Ingvartsen, C. Ferris, M. Hostens, M. A. Crowe, The GplusE consortium

Research output: Contribution to journalArticlepeer-review

Abstract

Homeorhetic mechanisms assist dairy cows to transition from pregnancy to lactation. Less successful cows develop severe negative energy balance (NEB), placing them at risk of metabolic and infectious disease and reduced fertility. We have previously placed multiparous Holstein Friesian cows from four herds into metabolic clusters, using as biomarkers measurements of plasma non-esterified fatty acids, β-hydroxybutyrate, glucose and IGF-1 collected at 14 and 35 d in milk (DIM). This study characterised the global transcriptomic profiles of liver and circulating leukocytes from the same animals to determine underlying mechanisms associated with their metabolic and immune function. Liver biopsy and whole blood samples were collected around 14 DIM for RNA sequencing. All cows with available RNAseq data were placed into balanced (BAL, n = 44), Intermediate (n = 44) or imbalanced (IMBAL, n = 19) metabolic cluster groups. Differential gene expression was compared between all three groups using ANOVA, but only the comparison between BAL and IMBAL cows is reported. Pathway analysis was undertaken using DAVID Bioinformatic Resources. Milk yields did not differ between BAL and IMBAL cows but the dry matter intake was less in IMBAL cows and they were in greater energy deficit at 14 DIM (-4.48 v -11.70 MJ/d for BAL and IMBAL cows). Significantly differentially expressed pathways in hepatic tissue included AMPK signalling, glucagon signalling, adipocytokine signalling and insulin resistance. Genes involved in lipid metabolism and cholesterol transport were more highly expressed in IMBAL cows but IGF1 and IGFALS were downregulated. Leukocytes from BAL cows had greater expression of histones and genes involved in nucleosomes and cell division. Leukocyte expression of heat shock proteins increased in IMBAL cows, suggesting an unfolded protein response, and several key genes involved in immune responses to pathogens were upregulated (e.g. DEFB13, HP, OAS1Z, PTX3 and TLR4). Differentially expressed genes upregulated in IMBAL cows in both tissues included CD36, CPT1, KFL11 and PDK4, all central regulators of energy metabolism. IMBAL cows therefore had greater difficulty maintaining glucose homeostasis combined with dysregulated hepatic lipid metabolism. Their energy deficit was associated with reduced capacity for cell division and greater evidence of stress responses in the leukocyte population, likely contributing to an increased risk of infectious disease
Original languageEnglish
JournalJournal of Dairy Science
Volume104
Issue number3
DOIs
Publication statusPublished - 14 Jan 2021

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