Novel Facets of the Liver Transcriptome Are Associated with the Susceptibility and Resistance to Lipid-Related Metabolic Disorders in Periparturient Holstein Cows

Figures

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  Figure 1. Body weight (panels a and b), body condition score (BCS; panels c and d), and calculated energy balance (panels e and f) for dairy cows clustered based on postpartum lipid metabolites within the original dietary treatment. Left-hand panels compare cows less (LS) or (MS) susceptible to lipid-related metabolic disorders, while right-hand panels compare cows more (MR) or less (LR) resistant to lipid-related metabolic disorders (n = 3 cows per cluster). Data are presented as least squares means (points) and their 95% confidence intervals (error bars); the exceptions are the arithmetic mean and 95% confidence interval for the −28 DRTC timepoint covariates (panels a–d). Statistics for the fixed effects of cluster, day relative to calving (DRTC), and their interaction (C × D) across the experimental period (panels a–d) or the postpartum period (panels e and f) are displayed in the top-right corner of each panel. Significant (*, p ≤ 0.05; Bonferroni adjusted) or marginal evidence (†, p = 0.07; Bonferroni adjusted) for the effects of cluster within DRTC or contrast of cluster across postpartum samples (bracketed) are indicated within their respective panels.

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  Figure 2. Blood fraction concentrations of glucose (panel a), fatty acids (FA; panel b), and β-hydroxybutyrate (BHB; panel c) for dairy cows less (LS) or more (MS) susceptible to lipid-related metabolic disorders (n = 3 cows per cluster). Data are presented as least squares means (points) and their 95% confidence intervals (error bars). Statistics for the fixed effects of cluster, day relative to calving (DRTC), and their interaction (C × D) are displayed in the top-right corner of each panel. Contrasts of cluster across postpartum samples did not reveal additional evidence of differences (p > 0.10; panels a and b).

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  Figure 3. Liver triglyceride (TG) content for dairy cows clustered based on postpartum lipid metabolites within the original dietary treatment. Panel (a) depicts cows less (LS) or more (MS) susceptible to lipid-related metabolic disorders, while panel (b) compares cows more (MR) or less (LR) resistant to lipid-related metabolic disorders (n = 3 cows per cluster). Data are presented as least squares means (points) and their 95% confidence intervals (error bars). Statistics for the fixed effects of cluster, day relative to calving (DRTC), and their interaction (C × D) are displayed in the top-right corner of each panel. Significant evidence (*, p ≤ 0.02; Bonferroni adjusted) for simple effects of cluster within DRTC are indicated in their respective panels.

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  Figure 4. Blood fraction concentrations of glucose (panel a), fatty acids (FA; panel b), and β-hydroxybutyrate (BHB; panel c) for dairy cows more resistant (MR) or less (LR) resistant to lipid-related metabolic disorders (n = 3 cows per cluster). Data are presented as least squares means (points) and their 95% confidence intervals (error bars). Statistics for the fixed effects of cluster, day relative to calving (DRTC), and their interaction (C × D) are displayed in the top-right corner of each panel. Marginal evidence (†; p = 0.07, panel a; p = 0.06, panel b) for contrasts of cluster across postpartum samples (bracketed) are indicated within their respective panels.

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  Figure 5. A working model of differentially regulated metabolic pathways in the liver of dairy cows that contribute to the pathology of lipid-related metabolic disorders. Fatty acids (FA) entering the hepatocyte are oxidized in the mitochondria (MITO) and peroxisomes (POX), producing energy and reactive oxygen species (ROS). Interferon (IFN) production is promoted by ROS, stimulating major histocompatibility complex (MHC) expression. Antigens (ANT) are oxidized (ANT●) by ROS. The ANT● are presented by the MHC promoting CD4+ T lymphocyte recruitment and cytokine (CK) production. Eicosanoids (EC) are formed by FA oxidation by ROS, and may promote ROS production. Glutathione (GSH) reduces ROS and other oxidized products. Arrows demonstrate the directionality and specificity of metabolic pathways: pathways not differentially regulated are grey dashed lines (----), pathways upregulated in cows less resistant to LRMD are blue (⸺⸺), pathways upregulated in cows less susceptible to LRMD are red (⸺⸺), and pathways generally upregulated in cows less susceptible and less resistant are solid black (⸺⸺).