Hyperinsulinemia: does it tip the balance toward intrahepatic fat accumulation?
Hodson L., Karpe F.
In health, the liver is metabolically flexible over the course of the day, as it undertakes a multitude of physiological processes including the regulation of intrahepatic and systemic glucose and lipid levels. The liver is the first organ to receive insulin and through a cascade of complex series of steps, insulin not only plays a key role in the intrahepatic regulation of glucose and lipid metabolism but also in the regulation of systemic glucose and lipid concentrations. Thus, when intra-hepatic insulin signalling becomes aberrant then this may lead to perturbations in intra-hepatic metabolic processes that have the potential to impact on metabolic health. For example, obesity is associated with intra-hepatic fat accumulation (known as non-alcoholic liver disease (NAFLD)) and hyperinsulinaemia, the latter as a result of insulin hypersecretion or impaired hepatic insulin extraction. Although insulin signalling directly alters intra- and extra-hepatic metabolism, the regulation of hepatic glucose and fatty acid metabolism is also indirectly driven by substrate availability. Here we discuss the direct and indirect effects of insulin on intrahepatic processes such as the synthesis of fatty acids and peripherally regulating the flux of fatty acids to the liver; processes that may play a role in the development of insulin resistance and/or IHTAG accumulation in humans.