Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Molecular Genetics, The University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Commun. 2021 Jun 18;12(1):3756. doi: 10.1038/s41467-021-23958-4.
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 H incorporation into fatty acids following deuterated water (HO) administration. However, the sensitivity of this approach is limited by the natural abundance of C, which masks detection of H by mass spectrometry. Here we report that high-resolution Orbitrap gas-chromatography mass-spectrometry resolves H and C fatty acid mass isotopomers, allowing DNL to be quantified using lower HO doses and shorter experimental periods than previously possible. Serial measurements over 24-hrs in mice detects the nocturnal activation of DNL and matches a 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, H specific MS provides the ability to study DNL in settings that are currently impractical.
从头合成脂肪生成（DNL）在多种人类疾病中受到破坏。因此，如果能够快速、非侵入性地进行检测，DNL 的定量可能有助于深入了解其机制并指导干预措施。DNL 通量通常通过氘水（HO）给药后 H 掺入脂肪酸来测量。然而，这种方法的灵敏度受到 C 的天然丰度的限制，这掩盖了通过质谱法检测 H。在这里，我们报告高分辨率轨道阱气相色谱-质谱法可以解析 H 和 C 脂肪酸质量同量异位体，从而可以使用比以前更低的 HO 剂量和更短的实验时间来定量 DNL。在小鼠中进行 24 小时的连续测量可以检测到 DNL 的夜间激活，并与 DNL 基因激活的小鼠中的 H-水方法相匹配。最重要的是，在不到一个小时的时间内可以在 overnight-fasted 人类中检测到 DNL，并在 4 小时的研究中对进食做出反应。因此，H 特异性 MS 提供了在目前不切实际的情况下研究 DNL 的能力。
