Measurement of metabolic fluxes using stable isotope tracers in whole animals and human patients.

PURPOSE OF REVIEW: Metabolic flux analysis using stable isotope labeled substrates allows for the tracing of carbon, nitrogen, and hydrogen atoms through metabolic pathways and is an invaluable tool for investigating dynamic metabolic changes occurring in health and disease. Studies of flux analysis in vivo are more technically challenging than in vitro or ex vivo but provide a highly detailed view of organ and/or systemic metabolism. We review here recent efforts in studies of diet and nutrition, non-small cell lung cancer, ischemia/reperfusion injury, and hemorrhagic shock where in vivo flux analysis was utilized to analyze metabolic modulation.

RECENT FINDINGS: Recent technical strides in the field of metabolomics afford sensitive and quantitative in vivo measurements of metabolic fluxes. Stable isotope tracing with C-glucose, C, N-glutamine, C-propionate, and other substrates are used in combination or in parallel to investigate the interplays among central carbon metabolic pathways and many other areas of the metabolome.

SUMMARY: Stable isotope tracing in vivo provides opportunities to investigate physiological processes in the context of the whole animal. These approaches, often NMR spectroscopy or mass spectrometry (MS)-based, are growing in use and will likely find key applications in studying systemic disease, sports physiology, cancer metabolism, and personalized medicine.