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

Abstract

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.

Hyperketonemia Predictions Provide an On-Farm Management Tool with Epidemiological Insights

“…Retained pHYK cows had greater ME fat yield, yet this was not observed in culled pHYK cows in first and second lactations. This is an interesting finding, especially within context of the relative value verses harm of mobilized fat during the transition period [ 29 , 30 , 53 ]. As discussed above, milk fat yield is a downstream reflector of mobilized fat but the contrasting pattern of retained verses culled cows suggests that the mobilized fat may not have been detrimental and could, as postulated above, be an aspect of coordinated energy partitioning.…”

“…When calculated, both fat-corrected and energy-corrected milk are greater in cows with HYK [ 23 ], which suggests that the impact of HYK on milk synthesis may reflect a shift in nutrient partitioning rather than generalized negative impacts on milk synthesis. Dynamic nutrient partitioning postpartum is a key component to optimizing metabolism and health [ 29 , 30 ]. Coordinated shifts to spare glucose may result in decreased milk yield while relying on the more abundant mobilized fat to maintain milk energy output.…”

Novel Facets of the Liver Transcriptome Are Associated with the Susceptibility and Resistance to Lipid-Related Metabolic Disorders in Periparturient Holstein Cows

“…Nevertheless, evidence for differences in lipid biomarkers-particularly liver TG and blood BHB-were found between clusters. Although nutrient partitioning is a normal physiological adaptation that may support feed efficiency, metabolic health, and productivity [46][47][48][49], dysregulation or imbalance can reflect metabolic disorders, which are the focus herein. Sequencing of the liver transcriptomes at several peripartum timepoints suggested numerous genes and metabolic pathways associated with LRMD at one or more timepoints.…”

The effects of prepartum energy intake and peripartum rumen-protected choline supplementation on hepatic genes involved in glucose and lipid metabolism

“…Both energy requirements and shared precursors closely link gluconeogenesis and FA oxidation (White, 2020). Regulation of many genes involved in FA oxidation is coordinated by transcription factors including peroxisome proliferator-activated receptor α (PPARα), which coordinates regulation of genes involved in oxidation via the tricarboxylic acid cycle, ketogenesis, and gluconeogenesis in cattle (Goselink et al, 2013).…”