Abstract

Hepatic gene expression profiling in cows with early postpartum ketosis using a bovine 13,000 oligonucleotide microarray 

J. J. Loor, R. E. Everts, H. M. Dann, D. E. Morin, S. L. Rodriguez-Zas, H. A. Lewin, and J. K. Drackley.  University of Illinois, Urbana.

ADSA/ASAS/CSAS Annual Joint Meeting, Cincinnati, July 24-28, 2005

We used a simple model for induction of ketosis (K) in early postpartum Holstein cows to examine liver gene expression profiles. Cows had ad libitum (142% of NRC requirements) or restricted (85% of requirements) DMI during the dry period. All cows were fed a common lactation diet after parturition. At 4 DIM, 7 cows classified as healthy after a physical examination were fed at 50% of DMI at d 4 from d 5 to signs of K or until 14 DIM. Another group of 7 healthy cows served as controls (H). Liver was biopsied at 10-14 (K) or 14 DIM (H). A 13,257 unique oligonucleotide (70-mers) array was used for transcript profiling. Annotation was based on similarity searches using BLASTN and TBLASTX against human, mouse, and bovine UniGene databases, the human genome, and the cattle TIGR database. Cy3- and Cy5-labelled cDNA from liver and a reference standard were used for hybridizations (28 microarrays). Loess-normalized log-transformed ratios were used to detect differential expression. ANOVA using a False Discovery Rate of P = 0.20 identified 3,513 differentially expressed genes. Hierarchical clustering of those genes showed that relative expression between K and H differed by 37%. Ketosis resulted in 76 downregulated genes with expression levels 2-fold or higher. There were 37 upregulated genes with K showing expression levels 2-fold or higher. Genes with key functions in stress, inflammation, and signal transduction had <2-fold expression in cows with K. Ketosis resulted in >2-fold decrease in expression for 2 genes involved in fatty acid desaturation, 2 in acetyl-CoA metabolism, and 1 in intracellular triglyceride transport. Other downregulated genes (>1.5-fold) in K were associated with regulation of transcription, insulin signaling, cytokine-mediated signaling, urea cycle/metabolism, and gluconeogenesis. Our data show that altered hepatic function due to ketosis postpartum is associated with complex changes in transcript expression patterns. Journal of Dairy Science, 88(Suppl. 1):195.