Endocrine Abstracts

Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. It remains unclear why intra-hepatocellular fat starts to accumulate, but it is likely to involve an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and triglyceride export from the liver. Studying hepatic metabolism in humans is challenging as direct assessment can only be achieved by arterio-venous difference measurements, which are impractical in humans due to the inaccessibility of the portal vein. By using a combination of models and methodologies, such as in vitro cellular models and stable isotope tracers, there is the potential to gain insight into intra-hepatocellular lipid metabolism. Humans spend the majority of the day in a postprandial, rather than postabsorptive state and when dietary fat and carbohydrates are consumed, a series of complex metabolic processes ensures that these nutrients are absorbed, transported around the body and stored appropriately. As the liver plays a major role in regulating fat and carbohydrate metabolism, perturbations in these metabolic processes have the potential to impact on metabolic health. For example, whether fatty acids are partitioned toward oxidation or esterification pathways appears to be dependent on a number of metabolic factors; not least ambient insulin concentrations. Moreover, the nutrient content of the diet appears to play a key role in intrahepatic fatty acid partitioning. This talk will review insights gained from undertaking studies using in vivo, ex vivo and in vitro models of human liver metabolism and discuss how metabolic and nutritional state may alter hepatic fatty acid partitioning. The usefulness of these models in understanding the aetiology and development of NAFLD will be highlighted.