Wilkinson Daniel J, Brook Matthew S, Smith Ken
MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, NIHR Nottingham BRC, UK.
Division of Health Sciences and Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, UK.
Clin Nutr Open Sci. 2021 Apr;36:111-125. doi: 10.1016/j.nutos.2021.02.005.
The key to understanding the mechanisms regulating disease stems from the ability to accurately quantify the dynamic nature of the metabolism underlying the physiological and pathological changes occurring as a result of the disease. Stable isotope tracer technologies have been at the forefront of this for almost 80 years now, and through a combination of both intense theoretical and technological development over these decades, it is now possible to utilise stable isotope tracers to investigate the complexities of in vivo human metabolism from a whole body perspective, down to the regulation of sub-nanometer cellular components (i.e organelles, nucleotides and individual proteins). This review therefore aims to highlight; 1) the advances made in these stable isotope tracer approaches - with special reference given to their role in understanding the nutritional regulation of protein metabolism, 2) some considerations required for the appropriate application of these stable isotope techniques to study protein metabolism, 3) and finally how new stable isotopes approaches and instrument/technical developments will help to deliver greater clinical insight in the near future.
理解疾病调控机制的关键在于能够准确量化疾病所导致的生理和病理变化背后新陈代谢的动态本质。近80年来,稳定同位素示踪技术一直处于这一领域的前沿。经过几十年来深入的理论和技术发展,现在可以利用稳定同位素示踪剂从全身角度研究体内人类新陈代谢的复杂性,直至亚纳米级细胞成分(即细胞器、核苷酸和单个蛋白质)的调控。因此,本综述旨在强调:1)这些稳定同位素示踪方法取得的进展——特别提及它们在理解蛋白质代谢的营养调控方面的作用;2)应用这些稳定同位素技术研究蛋白质代谢时需要考虑的一些因素;3)最后,新的稳定同位素方法以及仪器/技术发展将如何在不久的将来有助于提供更深入的临床见解。