Endocrine Abstracts

The liver is a relay station for fatty acid metabolism. Perturbations in hepatic fatty acid metabolism have the potential to impact widely on metabolic health. The accumulation or loss of liver fat (hepatocyte triacylglycerol (TG)) represents the balance between input pathways and removal pathways. In health these pathways must be closely balanced; imbalance will lead to changes in liver fat content. The concept of hepatic fatty acid partitioning is that fatty acids within the hepatocyte are broadly partitioned between two pathways: i) esterification to form mainly TG that will enter a hepatic TG pool and may be secreted as very low-density lipoprotein (VLDL)-TG, and ii) oxidation. In addition, the liver has the capacity for de novo lipogenesis (DNL).

Studying hepatic fatty acid partitioning in humans, in vivo, is challenging. Direct assessment of the liver can only be achieved by arterio-venous difference measurements, which is impractical in humans due to the inaccessibility of the portal vein. The use of stable isotope tracers and measurement of particles or molecules secreted by the liver such as VLDL-TG and 3-hydroxybutyrate (3-OHB) offers, at this point in time, the best insight into hepatic fatty acid metabolism in humans and have help advance our understanding.

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. Insulin undoubtedly regulates the supply of fatty acids to the liver from adipose tissue, however, whether chronic hyperinsulinaemia has a direct intra-hepatic effect on hepatic fatty acid partitioning, in humans, remains unclear. Hepatic fatty acid partitioning in humans has been investigated in the postabsorptive and postprandial states. This talk will discuss how the synthesis and partitioning of fatty acids within the liver may alter with metabolic and nutritional state.