Integrative Analyses of Hepatic Differentially Expressed Genes and Blood Biomarkers during the Peripartal Period between Dairy Cows Overfed or Restricted-Fed Energy Prepartum

Abstract

Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA). Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake [overfed (OF) or restricted (RE)] on liver of dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs. OF led to greater prepartal liver distress accompanied by a low-grade inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and creatinine). Post-partum the greater bilirubinaemia and lipid accumulation in OF vs. RE indicated a large degree of liver distress. The re-analysis of microarray data revealed that expression of >4,000 genes was affected by diet × time. The bioinformatics analysis indicated that RE vs. OF cows had a liver with a greater lipid and amino acid catabolic capacity both pre- and post-partum while OF vs. RE cows had a greater activation of pathways/functions related to triglyceride synthesis. Furthermore, RE vs. OF cows had a larger (or higher capacity to cope with) ER stress likely associated with greater protein synthesis/processing, and a higher activation of inflammatory-related functions. Liver in OF vs. RE cows had a larger cell proliferation and cell-to-cell communication likely as a response to the greater lipid accumulation. Analysis of upstream regulators indicated a pivotal role of several lipid-related transcription factors (e.g., PPARs, SREBPs, and NFE2L2) in priming the liver of RE cows to better face the early postpartal metabolic and inflammatory challenges. An all-encompassing dynamic model was proposed based on the findings.

The effect of calving in the summer on the hepatic transcriptome of Holstein cows during the peripartal period

“…Serum amyloid A is immediately secreted from liver after an inflammatory response (Faty et al, 2012); that is, it is a major APP that binds to toxins and helps clear lipoproteins out of the liver (Malle et al, 1993). Concentration of HP is also increased due to inflammation in the liver (Shahzad et al, 2014). Similarly, HAMP expression is increased shortly after acute inflammatory stimuli (Pigeon et al, 2001;Nicolas et al, 2002), supporting a role for hepcidin as a positive acute-phase response peptide in dairy cattle.…”

“…For instance, it is well established that the plane of energy nutrition during the dry period can influence the hepatic transcriptome and alter tissue function Shahzad et al, 2014). Because of the well-established decrease in DMI induced by heat stress, it is likely that cows calving in the summer (SU) compared with spring (SP) would experience more pronounced decreases in DMI leading to consequent changes in the hepatic transcriptome.…”

049 Physiological and molecular mechanisms associated with performance, immunometabolic status, and liver function in transition dairy cows fed rumen-protected methionine or choline

“…For instance, microarray analysis from our group revealed a greater overall subclinical inflammatory-like condition in feed-restricted cows compared with overfed cows (Shahzad et al, 2014).…”

Transcriptome-Wide Analysis Reveals the Role of PPARγControlling the Lipid Metabolism in Goat Mammary Epithelial Cells

“…Data were mined by an integrative systems biology approach applying the newly developed Dynamic Impact Approach (DIA) [24] and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA) [14]. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) biological process category database of bovine were used for functional analysis with the DIA.…”

“…It has been widely used in the bovine to study the differential gene expression among different treatments or physiological conditions [14–16]. Structural genomic studies of domestic animals have indicated that goats are closely related to bovine species [17].…”