The liver is a key metabolic organ that undertakes a multitude of physiological processes. It serves as an intermediary organ between exogenous (dietary) and endogenous energy supply to extrahepatic organs, with hepatocytes rapidly transitioning back and forth between the metabolic tasks of energy storage and supply. Given its pivotal role in regulating systemic metabolism, perturbations in hepatic metabolism can impact on metabolic disease risk. For example, the accumulation of intra-hepatocellular triglyceride (IHTG), which likely results from an imbalance between fatty acid delivery to the liver, hepatic fatty acid synthesis and fatty acid removal (via oxidation or export as triglyceride (TG)) from the liver.

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 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