Measurement of lipogenic flux by deuterium resolved mass spectrometry

Xiaorong Fu, Stanisław Deja, Justin A. Fletcher, Norma N. Anderson, Monika Mizerska, Gonçalo Vale, Jeffrey D. Browning, Jay D. Horton, Jeffrey G. McDonald, Matthew A. Mitsche and Shawn C. Burgess ()
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Xiaorong Fu: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Stanisław Deja: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Justin A. Fletcher: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Norma N. Anderson: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Monika Mizerska: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Gonçalo Vale: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Jeffrey D. Browning: The University of Texas Southwestern Medical Center
Jay D. Horton: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Jeffrey G. McDonald: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Matthew A. Mitsche: Center for Human Nutrition, The University of Texas Southwestern Medical Center
Shawn C. Burgess: Center for Human Nutrition, The University of Texas Southwestern Medical Center

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract De novo lipogenesis (DNL) is disrupted in a wide range of human disease. Thus, quantification of DNL may provide insight into mechanisms and guide interventions if it can be performed rapidly and noninvasively. DNL flux is commonly measured by 2H incorporation into fatty acids following deuterated water (2H2O) administration. However, the sensitivity of this approach is limited by the natural abundance of 13C, which masks detection of 2H by mass spectrometry. Here we report that high-resolution Orbitrap gas-chromatography mass-spectrometry resolves 2H and 13C fatty acid mass isotopomers, allowing DNL to be quantified using lower 2H2O doses and shorter experimental periods than previously possible. Serial measurements over 24-hrs in mice detects the nocturnal activation of DNL and matches a 3H-water method in mice with genetic activation of DNL. Most importantly, DNL is detected in overnight-fasted humans in less than an hour and is responsive to feeding during a 4-h study. Thus, 2H specific MS provides the ability to study DNL in settings that are currently impractical.

Date: 2021
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DOI: 10.1038/s41467-021-23958-4

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