ADSA Foundation Scholar Award: Influencing hepatic metabolism: Can nutrient partitioning be modulated to optimize metabolic health in the transition dairy cow?

Hepatic de novo production of glucose and oxidation of fatty acids are critical in supporting milk production during the transition to lactation period. During this period of metabolic challenge, there is an increase in fatty acids taken up by the liver. Although the primary fate for these fatty acids is complete oxidation, alternative fates include incomplete oxidation via ketogenesis, storage within the liver as triglycerides (TG), and secretion of TG within very low density lipoproteins. Influencing the relative capacity of these pathways, and thus shifting nutrient partitioning, may allow for improved hepatic efficiency and metabolic health. Hepatic nutrient partitioning reflects complex regulation of key metabolic pathways by factors such as fatty acids and other substrates. Relative flux of fatty acid through oxidation or re-esterification to TG leads to the onset of metabolic disorders that are associated with negative production outcomes, such as hyperketonemia and fatty liver. Although recent work has focused on understanding how stored TG are lipolyzed for subsequent oxidation, the mechanism and regulation of this remains unclear. The source of mobilized fatty acids is similarly important, both in terms of amount and profile of fatty acids mobilized. There is likely a complex, coordinated whole-body response, given that fatty acids mobilized from adipose tissue affect hepatic regulation. Fatty acids mobilized from adipose tissue have regulatory effects on genes such as pyruvate carboxylase; however, in vivo work suggests there may also be other influences resulting in differential regulation between cows that subsequently develop sub-clinical ketosis and those that do not. Optimizing nutrient partitioning between critical metabolic pathways may allow for nutritional opportunities to reduce incidence of metabolic challenges and improve feed efficiency. Although further research is needed to continue refining our understanding of the intricate balance regulating hepatic metabolism, shifting nutrient partitioning may be key in supporting both efficiency and metabolic health.