Stable isotope tracers and exercise physiology: Past, present and future

Abstract

Stable isotope tracers have been invaluable assets in physiological research for over 80 years. The application of substrate-specific stable isotope tracers has permitted exquisite insight into amino acid, fatty-acid and carbohydrate metabolic regulation (i.e. incorporation, flux, oxidation, and in a tissue-specific and whole-body fashion) in health, disease and in response to acute and chronic exercise. Yet, despite many breakthroughs, there are limitations to "substrate specific" stable isotope tracers, which limit physiological insight e.g. the need for I.V infusions and restriction to short term studies (hours) in controlled laboratory settings. In recent years significant interest has developed in alternative stable isotope tracer techniques that overcome these limitations; in particular deuterium oxide (D₂O or heavy water). The unique properties of this tracer mean that through oral administration, the turnover and flux through a number of different substrates (muscle proteins, lipids, glucose, DNA [satellite cells]) can be monitored simultaneously and flexibly (hours/weeks/months) without the need for restrictive experimental control. This makes it uniquely suited for the study of 'real world' human exercise physiology (amongst many other applications). Moreover, using D₂O permits evaluation of turnover of plasma/muscle proteins (e.g. dynamic proteomics) in addition to metabolomics (e.g. fluxomics) to seek molecular underpinnings e.g. of exercise adaptation. Herein, we provide insight into the role of stable isotope tracers, from substrate-specific to novel D₂O approaches, in facilitating our understanding of metabolism. Further novel potential applications of stable isotope tracers are also discussed in the context of integrating with the snowballing field of OMIC technologies.

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