Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling
Advances in stable isotope tracer methodology part 1: hepatic metabolism via isotopomer analysis and postprandial lipolysis modeling
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DOI：
10.1136/jim-2019-001109
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发表时间：
2020-01-01
影响因子：
2.6
通讯作者：
Cree-Green, Melanie
中科院分区：
文献类型：
--
作者：
Behn, Cecilia Diniz;Jin, Eunsook S.;Cree-Green, Melanie
稳定的同位素示踪剂已经被用来了解动物和人类的综合生理学。更常被研究的器官系统包括肝脏葡萄糖代谢、脂肪组织的脂肪分解和全身蛋白质代谢。最近同位素方法学的改进包括使用新的生理学方法/模型和对不同生理状态下的数据进行数学建模。在这里，我们回顾了该领域的一些最新进展，并强调了未来的研究需求。首先，我们讨论了使用口服[U-C-13(3)]-甘油示踪剂来确定甘油碳在第一次通过三羧酸循环、甘油进入戊糖磷酸途径或甘油直接转化为葡萄糖后对肝脏葡萄糖产生的相对贡献。其次，我们描述了已建立的用于定义餐后血糖动力学的口服最小模型的改进，以将甘油动力学包括在口服葡萄糖耐量试验中，并使用[H-2(5)]-甘油示踪剂来确定脂解的动态变化。当描述甘油通量的参数用基于示踪剂的计算和约束参数优化的混合方法确定时，模拟结果被优化。这两种方法不仅可以用来扩展我们对人体生理学的了解，还可以用来扩展各种营养策略和药物对新陈代谢的影响。
Stable isotope tracers have been used to gain an understanding of integrative animal and human physiology. More commonly studied organ systems include hepatic glucose metabolism, lipolysis from adipose tissue, and whole body protein metabolism. Recent improvements in isotope methodology have included the use of novel physiologic methods/models and mathematical modeling of data during different physiologic states. Here we review some of the latest advancements in this field and highlight future research needs. First we discuss the use of an oral [U-C-13(3)]-glycerol tracer to determine the relative contribution of glycerol carbons to hepatic glucose production after first cycling through the tricarboxylic acid cycle, entry of glycerol into the pentose phosphate pathway or direct conversion of glycerol into the glucose. Second, we describe an adaptation of the established oral minimal model used to define postprandial glucose dynamics to include glycerol dynamics in an oral glucose tolerance test with a [H-2(5)]-glycerol tracer to determine dynamic changes in lipolysis. Simulation results were optimized when parameters describing glycerol flux were determined with a hybrid approach using both tracer-based calculations and constrained parameter optimization. Both of these methodologies can be used to expand our knowledge of not only human physiology, but also the effects of various nutritional strategies and medications on metabolism.