De novo lipogenesis in non-alcoholic fatty liver disease: Quantification with stable isotope tracers

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 ² H 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 ¹³ C enrichment from a second tracer such as [U-¹³ C]sugar with minimal interference of one tracer with the other.

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.