Adipose and liver gene expression profiles in response to treatment with a nonsteroidal antiinflammatory drug after calving in grazing dairy cows

M. Vailati Riboni, S. Meier, N.V. Priest, C.R. Burke, J.K. Kay, S. McDougall, M.D. Mitchell, C.G. Walker, M. Crookenden, A. Heiser, J.R. Roche, J.J. Loor

The peripartal or transition period in dairy cattle is often characterized by an inflammatory state that, if not controlled, could be detrimental to production, health, and fertility. Approaches to control the postpartal degree of inflammation include treatments with nonsteroidal antiinflammatory drugs (NSAID) postcalving, which have improved cow production and health. To date, most of the research on NSAID has been conducted in confinement cows that reach milk production levels substantially greater than those on pasture. Furthermore, little data are available on the effect of NSAID on the mRNA expression of inflammation and metabolism-related genes. Transcription regulation is an important mechanism of inflammation and metabolic control. The present study was conducted to examine hepatic and adipose tissue gene expression in response to injections of an NSAID, carprofen, on 1, 3, and 5 d after calving. Grazing Holstein-Friesian cows from a control group and 1 treated with carprofen during the first 5 d postcalving were used. Liver and subcutaneous adipose tissue biopsies were harvested at -1, 1, and 2 wk relative to parturition. More than 30 genes associated with fatty acid oxidation, growth hormone/insulin-like growth factor-1 axis, hepatokines, lipoprotein metabolism, gluconeogenesis, and inflammation were analyzed. After calving, data suggest that both tissues respond to inflammation signals at the onset of lactation. Administration of NSAID led to greater hepatic expression of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which helps regulate gluconeogenesis, and microsomal triglyceride transfer protein (MTTP), important for the assembly and secretion of very low-density lipoproteins. In adipose tissue, NSAID administration resulted in greater expression of the inflammation-related genes interleukin-1, β (IL1B), interleukin-6 receptor (IL6R), toll-like receptor 4 (TLR4), and chemokine (C-C motif) ligand 5 (CCL5). The data support the role of inflammation as a normal component of the homeorhetic adaptations to lactation and reveal a possible mechanism of action of carprofen in transition dairy cows, but do not reflect an effect of this NSAID on the extent of the peripartum inflammation.