European journal of clinical investigation
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Eur. J. Clin. Invest. · Mar 2022
ReviewThe role of RIPK3 in liver mitochondria bioenergetics and function.
Receptor-interacting protein kinase 3 (RIPK3) is a key player of regulated necrosis or necroptosis, an inflammatory form of cell death possibly governing outcomes in chronic liver diseases, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. ⋯ Since mitochondrial dysfunction and RIPK3-mediated necroptosis are intimately involved in chronic liver disease pathogenesis, understanding the role of RIPK3 in mitochondrial bioenergetics and its potential translational application are of great interest.
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Eur. J. Clin. Invest. · Mar 2022
ReviewDe 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.