Abstract
As milk production in dairy cattle continues to increase, so do the energetic and nutrient demands on the dairy cow. An inability of the cow to make the necessary homeorhetic adjustments in metabolism not only impairs lactation performance but increases the risk of developing metabolic disorders. The physiological adaptations to lactation involve the mammary gland that produces milk and extramammary tissues that coordinately enhance the availability of precursors for milk synthesis. Changes in whole body metabolism and nutrient partitioning are accomplished, in part, through the bioenergetic and biosynthetic capacity of the mitochondria, providing energy and diverting important substrates to the mammary gland in support of lactation. With increased oxidative capacity and ATP production, reactive oxygen species (ROS) production in mitochondria may be altered. Imbalances between oxidant production and antioxidant activity can lead to oxidative damage to cellular structures and contribute to disease. Thus, mitochondria are tasked with meeting the energy needs of the cell while minimizing oxidative stress. Mitochondrial function is regulated in concert with cellular metabolism by the nucleus. With only a small number of genes present within the mitochondrial genome, many genes regulating mitochondrial function are housed in nuclear DNA. My thesis research describes the involvement of mitochondria in coordinating tissue-specific metabolic adaptations across lactation and assessment of mitochondrial-nuclear signaling pathways that regulate mitochondrial proliferation and function in response to shifting cellular energy need across lactation. We found liver mitochondrial efficiency was positively associated with milk yield. Given that circulating nonesterified fatty acids (NEFA) concentrations are also increased at the onset of lactation our findings suggest an increase in fat substrate use with increased coupling to ATP production. ROS emissions, as expected based on OXPHOS findings, also increased throughout lactation. Skeletal muscle mitochondrial function was more consistent across lactation and did not vary with milk production. We also observed oxidative damage in muscle tissue, possibly a result of proteolysis and amino acid mobilization for use by the mammary gland to synthesize milk.