Ketosis under a systems veterinary medicine perspective

Ketosis (hyperketonemia) is a prevalent metabolic disease of transition dairy cows that affects ~30-40% of the cows during early lactation. Cows with ketosis have lower milk yield and reproductive performance, greater risk of other periparturient diseases, and higher culling rates. Ketosis is characterized by an excess level of circulating ketone bodies with blood concentration of beta-hydroxybutyrate (BHBA) been recognized as a golden standard for diagnosis of the disease. However, the cutoff value for serum BHBA for diagnosis of ketosis appears to be somewhat arbitrary. Negative energy balance at early lactation is the primary hypothesis for the explanation of the pathobiology of ketosis. Treatment strategies are focused on maintenance of glucose and ketone body homeostasis. The exact causes and the etiopathology of ketosis remain incompletely understood. In some recent metabolomics studies, data show that the number of metabolites altered in the plasma/serum or milk and metabolic pathways perturbed during ketosis are numerous. It is obvious that ketone bodies and glucose metabolism are not the only perturbed metabolites during ketosis. Mounting evidence indicates that multiple alterations also occur at proteome, transcriptome, and genome levels and other component networks. Integration of all the knowledge generated by genomics, transcriptomics, proteomics, metabolomics, and lipidomics can help detect perturbations of biological information on distinct tiers and give insight on the causes and pathobiology of ketosis in dairy cows.