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，以科学为基础的饮食 充其量，建议仍然是一般性的和不完美的。要实现更具体、量身定制、 可靠的饮食指导是我们对食物在我们体内发生的事情缺乏了解。潜在的 从饮食碳水化合物到二氧化碳的简单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，而且还 由组织自身释放的代谢中间产物。这些循环营养素是如何促进 纸巾是燃料吗？每种循环营养物质是由哪些组织产生的？在这份提案中，我提议 利用体内同位素示踪和定量模拟系统地确定组织下沉和 哺乳动物体内循环营养物质的来源。在目标1中，我将重点放在组织上，并量化它们的燃料使用量 通过将同位素标记的营养物质追踪到其三氯乙酸循环中来研究循环营养物质。在目标2中，我将重点放在重要的 循环营养物质和量化其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法的差异测量。在成功完成后 我提出的研究，我们将更接近对能量的整体和定量的理解 哺乳动物的新陈代谢。这项工作将为最终提高对 饮食与健康的关系。这项建议还将使我能够成功过渡到 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.