title: 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.
authors.affiliation: 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.
authors.forename: Khuram
authors.initials: K
authors.lastname: Shahzad
authors.affiliation: Department of Animal and Rangeland Sciences, Oregon State University, Corvallis, Oregon, United States of America.
authors.forename: Massimo
authors.initials: M
authors.lastname: Bionaz
authors.affiliation: Istituto di Zootecnica and Centro di ricerca sulla nutrigenomica, Universitá Cattolica del Sacro Cuore, Piacenza, Italy.
authors.forename: Erminio
authors.initials: E
authors.lastname: Trevisi
authors.affiliation: Istituto di Zootecnica and Centro di ricerca sulla nutrigenomica, Universitá Cattolica del Sacro Cuore, Piacenza, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bertoni
authors.affiliation: 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.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Rodriguez-Zas
authors.affiliation: 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.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Loor
mesh_terms: D000824:Animal Nutritional Physiological Phenomena / Q000235:genetics*; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002417:Cattle; D003612:Dairying; D004032:Diet; D002149:Energy Intake; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D008099:Liver / Q000378:metabolism*; D008954:Models, Biological; D049590:Postpartum Period / Q000097:blood*; D011247:Pregnancy
chemical_list: D015415:Biomarkers