Novel facets of the liver transcriptome are associated with the susceptibility and resistance to lipid-related metabolic disorders in periparturient Holstein cows

Authors: PRALLE, RYAN - University Of Wisconsin; Li, Wenli; MURPHY, BRIANNA - Orise Fellow; HOLDORF, HENRY - University Of Wisconsin; WHITE, HEATHER - University Of Wisconsin

Submitted to: Animals
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/25/2021
Publication Date: 8/31/2021
Citation: Pralle, R., Li, W., Murphy, B., Holdorf, H.T., White, H. 2021. Novel facets of the liver transcriptome are associated with the susceptibility and resistance to lipid-related metabolic disorders in periparturient Holstein cows. Animals. 11(9). Article 2558. https://doi.org/10.3390/ani11092558.
DOI: https://doi.org/10.3390/ani11092558

Interpretive Summary: Energy and nutrient demands of the early lactation period can result in the development of metabolic disorders, such as ketosis and fatty liver, in dairy cows. Not all cows experience these disorders, which suggests some cows have an ability to adapt. The objective of this study was to discover differences in liver gene expression that are associated with a cow’s susceptibility (disposition to disorder during typical conditions) or resistance (disposition to disorder onset and severity when presented a challenge) to metabolic disorders. Cows in a control treatment and a ketosis-induction treatment were retrospectively grouped into susceptible and resistant groups, respectively, by a machine learning algorithm using lipid biomarker concentrations. Whole transcriptome RNA sequencing was performed on liver samples from these cows to assess gene expression. Differences in gene expression were observed among the different groups. The overall metabolism inferred from the gene expression suggests responses to oxidative stress may determine susceptibility and resistance to metabolic disorders, with novel implications for immunometabolism. These findings may ultimately contribute to management or other strategies to mitigate metabolic disorders in early-lactation dairy cows.

Technical Abstract: Lipid-related metabolic disorders (LRMD) are prevalent in early lactation dairy cows and have detrimental effects on productivity and health. Our objectives were to identify cows resistant or susceptible to LRMD using a ketosis induction protocol (KIP) to discover differentially expressed liver genes and metabolic pathways associated with disposition. Clustering cows based on postpartum lipid metabolite concentrations within dietary treatments identified cows more or less susceptible (MS versus LS) to LRMD within the control treatment, and more or less resistant (MR versus LR within the KIP treatment). Whole transcriptome RNA-sequencing was performed on liver samples (-28, +1, and +14 days relative to calving) to assess differential gene and pathway expression (LS versus MS, MR versus LR). Cows within the MS and LR clusters had greater concentrations of the lipid metabolites than LS and MR clusters. Inferred metabolism of differentially expressed genes suggested a role of immune response (i.e. interferon-inducible proteins and major histocompatibility complex molecules). Additionally, our data indicated unique roles for glutathione metabolism and eicosanoid metabolism for modulating susceptibility and resistance, respectively. Overall, this research provides novel insight into the role of immunometabolism in LRMD pathology and suggests potential for unique control points for LRMD progression and severity.