Coordination of energy metabolism across individual tissues in mammals

项目摘要 我们吃什么可能是我们健康的唯一最重要的决定因素。然而，基于科学的饮食 建议充其量仍然是一般性的和不完善的。一个根本的障碍是更具体，更有针对性， 可靠的饮食指导是我们对食物在我们体内发生的变化缺乏了解。所依据 从膳食碳到CO2的简单的整体化学反应是个体组织中不同的能量代谢。 组织从血液中获取燃料，血液不仅直接从消化中携带营养物质， 由组织自身释放的代谢中间产物。这些循环营养素如何有助于 组织作为燃料？每一种循环营养物质都是由哪些组织产生的？在这个提议中，我提议 使用体内同位素示踪和定量建模来系统地确定组织汇， 哺乳动物的循环营养来源。在目标1中，我将重点关注组织，并量化它们的燃料消耗， 通过追踪同位素标记的营养物质进入TCA循环来循环营养物质。在目标2中，我将重点关注重要的 循环营养素和量化他们的组织来源和汇的创新方法相结合， 同位素示踪剂输注和动静脉标记差异测量。成功完成后 我提出的研究，我们将更接近一个整体和定量的了解能源， 哺乳动物的新陈代谢。这项工作将为最终更好地了解 饮食与健康的关系这一建议也将使我能够成功地过渡到一个 独立调查员

Project Summary What we eat may be the single most important determinant of our health. Yet, science-based dietary recommendations remain, at best, generic and imperfect. One fundamental obstacle to more specific, tailored, and reliable dietary guidance is our lack of understanding of what happens to food in our body. Underlying the simple overall chemical reaction from dietary carbons to CO2 is diverse energy metabolism in individual tissues. Tissues take their fuels from the bloodstream, which carries not only nutrients directly from digestion but also metabolic intermediates released by tissues themselves. How do these circulatory nutrients contribute to tissues as fuels? And by which tissues is each of the circulatory nutrients produced? In this proposal, I propose to use in vivo isotopic tracing and quantitative modeling to systematically determine the tissue sinks and sources of circulatory nutrients in mammals. In Aim 1, I will focus on tissues and quantify their fuel usage from circulatory nutrients by tracing isotopic labeled nutrients into their TCA cycle. In Aim 2, I will focus on important circulatory nutrients and quantify their tissue sources and sinks by an innovative approach of combining isotopic tracer infusion and arteriovenous labeling difference measurements. Upon successful completion of my proposed research, we will move closer to a holistic and quantitative understanding of the energy metabolism in mammals. The work will lay the foundation for eventual improved understanding of the relationship between diet and health. This proposal will also allow me to successfully transition to an independent investigator.