Tracer-Based Metabolic Analysis by NMR in Intact Perfused Human Liver Tissue

Human metabolic liver disease is dramatically increasing globally and presents an urgent clinical unmet need. Rodent models of non-alcoholic fatty liver disease (NAFLD) are available, but they fail to fully recreate the metabolic and cellular features of human disease. Thus, it is imperative to understand the metabolic interplay in human cells in the context of disease. We have applied nuclear magnetic resonance (NMR) spectroscopy approaches to enable the detection of numerous metabolites in human cells and within intact tissue in a single measurement. In this chapter, we describe the challenges of using isolated human hepatocytes vs perfused human liver tissue for metabolic tracer experiments and how experimental parameters can be refined to interrogate signals from intact tissue and cells.