Fatty Acids to Minimize Hepatic Lipidosis in Dairy Cows - Genomic adaptations in bovine Liver 

Funded by Section 1433 - Animal Health & Disease (ILLU-538-952, 2006-2007)

Objectives: The overall objective is to determine the molecular mechanisms underlying fatty liver and the potential use of dietary fatty acids as preventatives for this disease in dairy cows experiencing excessive drops in feed intake soon after calving. We will use functional genomics tools to compare gene expression profiles in liver tissue from cows in negative energy balance with marked elevations of blood NEFA and receiving different unsaturated fatty acids treatments to identify disease-specific genes that may play crucial roles in the etiology and prevention of fatty liver. Our hypothesis is that fatty acids, depending on their degree of unsaturation, play a role in the concerted activation of peroxisome proliferator activated receptor-alpha (PPAR-alpha) and peroxisome proliferator activated receptor co-activator gamma-1A (PPARGC1A) in bovine liver, which in turn results in down-stream activation of genome-wide transcriptional events causing differential expression of genes associated with regulation of various aspect of cell growth and differentiation, regulation of tissue physiological processes, and metabolism. These molecular events are essential to maintain or increase fatty acid oxidation (i.e., prevent lipidosis) and glucose production, and to prevent oxidative stress and liver inflammation.

Specific objectives are 1) To determine global gene expression patterns in liver tissue in response to a simultaneous elevation of NEFA influx into liver and infusion of specific polyunsaturated fatty acids as preventatives of fatty liver, and 2) To determine global gene expression patterns in liver tissue slices in response to incremental concentrations of polyunsaturated fatty acids and 3) To relate liver gene expression profiles with other physiological measurements associated with metabolic responses to negative energy balance and elevated blood NEFA.

Potential benefits:  Fatty liver afflicts 50% of the cows that calve and is a costly disease to animal agriculture. Dairy cows are most susceptible to fatty liver and ketosis during the first 4 weeks post-partum. Furthermore, liver lipidosis is associated with nearly all other periparturient metabolic problems. Around calving, cows experience a period of negative energy balance that may contribute to fatty liver and ketosis. Our liver-insult model will allow us to examine the molecular and cellular basis of the responsiveness to different fatty acids in the bovine liver during negative energy balance and the ensuing acute elevation in the delivery of NEFA to liver. Determining the relationships between fatty acids varying in the degree of unsaturation, and the liver tissue response to excessive concentrations of NEFA, which often result in fatty liver, might lead to better recommendations for nutrition and management during the dry period to prevent or decrease susceptibility to fatty liver and ketosis soon after calving. These studies represent an important benchmark for work in this area, and will be a major advancement in our knowledge of nutrient-gene interactions and disease. Identification of specific genome sequences that predispose susceptibility/resistance to disease, or respond to specific nutrients will be fundamental to advancing animal health and well-being within the dairy industry in Illinois and beyond. The end result will be increased profitability of dairy enterprises.