Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 Jun 10;9(6):e99757. doi: 10.1371/journal.pone.0099757. eCollection 2014.

Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

Author information

1
Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.
2
Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, Oregon, United States of America.
3
Istituto di Zootecnica and Centro di ricerca sulla nutrigenomica, Universitá Cattolica del Sacro Cuore, Piacenza, Italy.
4
Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America; The Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America.

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.

PMID:
24914544
PMCID:
PMC4051754
DOI:
10.1371/journal.pone.0099757
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center