Collaborative Research: Inflammation as a Key Component of the Metabolic Adaptations to the Lactating State

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The immune system is responsible for defending the body against pathogens and mediating the responses to some injuries through inflammatory processes. Inflammation can also impact metabolism and energy use. This award will support studies to test whether the non-defensive roles of the immune system are necessary for the metabolic transitions that occur with the onset of lactation, a period when energy use in an animal undergoes extreme changes. The question will be assessed through the use of non-steroidal anti-inflammatory drug administration at the start of lactation in cattle because they are well suited for these studies and are very tractable experimental systems. This project will support research training for under-represented students at the nexus of biology, agriculture, and medicine, provide unique experience for several advanced trainees, and generate transformative information relevant to a broad spectrum of the public. Under-represented students will be recruited to participate in the entire research process, from treatment application to presentation of results. A post-doctoral associate and PhD students will also be mentored. Additional societal benefit may be afforded by utilization of the basic research results for the development of applied management strategies in agriculture.The objective of this research is to assess whether endogenous inflammation in early lactation is necessary to induce insulin resistance and conserve glucose as nutrient demands for the mammary gland increase. Basal and insulin-stimulated glucose kinetics, as well as liver, muscle, and adipose tissue markers of inflammation and insulin signaling will be measured in cows at high and low milking frequency. Milking frequency will alter milk yield, allowing for the assessment of whether inflammation-mediated homeorhetic processes are particularly important for supporting extreme milk yields. By blocking endogenous low-grade inflammation in early lactation, anti-inflammatory treatment is expected to increase insulin sensitivity, resulting in increased muscle and adipose tissue utilization of glucose, suppressed liver gluconeogenesis, and impaired regulation of plasma glucose concentration in early lactation. Results from the studies will be disseminated through peer-reviewed journals and through presentations at scientific meetings.