De novo lipogenesis in non-alcoholic fatty liver disease: Quantification with stable isotope tracers
De novo lipogenesis in non-alcoholic fatty liver disease: Quantification with stable isotope tracers
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DOI：
10.1111/eci.13733
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发表时间：
2022-01-04
影响因子：
5.5
通讯作者：
Jones, John G.
中科院分区：
文献类型：
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作者：
Belew, Getachew Debas;Jones, John G.
背景：非酒精性脂肪性肝病（NAFLD）的特征是肝细胞中甘油三酯的异常积累。肝脏新生脂肪生成可能在NAFLD期间肝脏脂质积累中起重要作用。由于脂质生物合成通量在NAFLD和T2D中的重要性，已经开发了示踪剂方法来研究和量化它们。在这里，我们提出了使用稳定同位素示踪剂测量和量化DNL的新方法。在动物模型和人类中，氘化水是一种广泛用于量化DNL率的示踪剂。(2)H2O中脂质氢的富集可以通过分离的脂质H-2核磁共振和质谱分析来分辨和定量。与质谱相比，核磁共振提供了更高水平的位置富集信息，从而产生了更详细的脂质生物合成图像。它还可以用于定量低水平的脂质C-13富集，从第二种示踪剂，如[U-C-13]糖，一个示踪剂与另一个干扰最小。尽管DNL活性升高与肝脏甘油三酯水平升高之间存在明显的关联，但实施非破坏性和新颖的方法来量化DNL及其对NAFLD的贡献也引起了极大的兴趣。
Background Non-alcoholic fatty liver disease (NAFLD) is characterized as an abnormal accumulation of triglyceride in hepatocytes. Hepatic de novo lipogenesis may play an important role in the accumulation of lipids in the liver during NAFLD. Due to the importance of lipid biosynthetic fluxes in NAFLD and T2D, tracer methodologies have been developed for their study and quantification. Here, we address novel approaches to measure and quantify DNL using stable isotope tracers. Deuterated water is a widely used tracer for quantifying DNL rates in both animal models and humans. Enrichment of lipid hydrogens from (2)H2O can be resolved and quantified by H-2 NMR and MS spectroscopy of isolated lipids. NMR provides a much higher level of positional enrichment information compared with MS which yields a more detailed picture of lipid biosynthetic. It can also be used to quantify low levels of lipid C-13 enrichment from a second tracer such as [U-C-13]sugar with minimal interference of one tracer with the other. Conclusions Despite the clear association between elevated DNL activity and increased hepatic triglyceride levels, implementation of non-destructive and novel methods to quantify DNL and its contribution to NAFLD are also of huge interest.