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

ScholarsArchive at Oregon State University

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Title Integrative Analyses of Hepatic Differentially Expressed Genes and Blood Biomarkers during the Peripartal Period between Dairy Cows Overfed or Restricted-Fed Energy Prepartum
Names Shahzad, Khuram (creator)
Bionaz, Massimo (creator)
Trevisi, Erminio (creator)
et al. (creator)
Date Issued 2014-06-10 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by the Public Library of Science. The published article can be found at: http://www.plosone.org/.
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 x 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.
Genre Article
Access Condition http://creativecommons.org/licenses/by/3.0/us/
Identifier Shahzad K, Bionaz M, Trevisi E, Bertoni G, Rodriguez-Zas SL, et al. (2014) Integrative Analyses of Hepatic Differentially Expressed Genes and Blood Biomarkers during the Peripartal Period between Dairy Cows Overfed or Restricted-Fed Energy Prepartum. PLoS ONE 9(6): e99757. doi:10.1371/journal.pone.0099757

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