Nutrition-induced ketosis alters metabolic and signaling gene networks in liver of periparturient dairy cows. Bos taurus

Hepatic molecular adaptations underlying periparturient metabolic diseases such as ketosis in dairy cows are largely unknown. We used a simple model for induction of ketosis to examine liver gene expression profiles using a microarray consisting of 13,257 annotated cattle oligonucleotides. At 4 days post-partum, 7 cows classified as healthy after a physical examination were fed at 50% of intake at day 4 from day 5 to signs of ketosis or until 14 days post-partum. Another group of 7 healthy cows served as controls. Liver was biopsied at 9-14 (ketosis) or 14 days post-partum (controls). More than 9,000 sequences represented on the microarray were expressed in liver. Keywords: disease state analysis Overall design: Fourteen multiparous Holstein cows classified as healthy after a thorough physical examination on day 4 postpartum were randomly assigned to a healthy control group or to a ketosis induction group. Ketosis induction was by feed restriction. At 5 days postpartum cows in the ketosis induction group were fed at 50% of their intake at 4 days post-partum until signs of clinical ketosis (anorexia, ataxia, or abnormal behavior) or until 14 days postpartum, and then were returned to ad libitum intake and treated, if necessary. Total RNA from liver and a reference standard (derived from cattle tissues) was extracted and labelled with Cy3 and Cy5 in a dye-swap design. Samples were co-hybridize for 48 hours to microarrays containing 13,257 elements.