Measurement of lipogenic flux by deuterium resolved mass spectrometry

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 (2)H incorporation into fatty acids following deuterated water ((2)H(2)O) administration. However, the sensitivity of this approach is limited by the natural abundance of (13)C, which masks detection of (2)H by mass spectrometry. Here we report that high-resolution Orbitrap gas-chromatography mass-spectrometry resolves (2)H and (13)C fatty acid mass isotopomers, allowing DNL to be quantified using lower (2)H(2)O doses and shorter experimental periods than previously possible. Serial measurements over 24-hrs in mice detects the nocturnal activation of DNL and matches a (3)H-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, (2)H specific MS provides the ability to study DNL in settings that are currently impractical.