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

免疫系统负责保护身体免受病原体的侵害，并通过炎症过程介导对某些损伤的反应。 炎症也会影响新陈代谢和能量使用。 该奖项将支持研究，以测试免疫系统的非防御性作用是否是必要的代谢转变发生在哺乳期的开始，一个时期，在动物的能量使用经历了极端的变化。 将通过在牛泌乳开始时使用非甾体抗炎药来评估该问题，因为它们非常适合这些研究，并且是非常易于处理的实验系统。 该项目将支持在生物学，农业和医学的关系代表性不足的学生的研究培训，为几个高级学员提供独特的经验，并产生相关的广泛的公众变革信息。 代表性不足的学生将被招募参与整个研究过程，从治疗应用到结果展示。 博士后助理和博士生也将得到指导。 利用基础研究成果发展农业应用管理战略，还可带来额外的社会效益，本研究的目的是评估泌乳早期内源性炎症是否是诱导胰岛素抵抗和保护葡萄糖作为乳腺营养需求增加所必需的。将在高和低挤奶频率下测量奶牛的基础和胰岛素刺激葡萄糖动力学，以及肝脏、肌肉和脂肪组织炎症和胰岛素信号传导标志物。挤奶频率将改变产奶量，从而评估炎症介导的顺势过程是否对支持极端产奶量特别重要。通过阻断泌乳早期的内源性低度炎症，预期抗炎治疗可增加胰岛素敏感性，导致肌肉和脂肪组织对葡萄糖的利用增加，抑制肝脏再生，并损害泌乳早期血糖浓度的调节。 研究结果将通过同行评审期刊和在科学会议上的介绍加以传播。

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.