Mechanisms of Dietary Fructose and Copper in the Development and Progression of NAFLD Spectrum Disorders

Abstract

Dietary induced oxidative stress appears to be factor which affects the development and progression of non‐alcoholic fatty liver disease (NAFLD) spectrum disorders, however no clear mechanism(s) for this have been identified. Preliminary studies by the Burkhead lab and others suggest that exposure to high oxidative stresses through the diet, lowers hepatic copper import even in copper deeffiecnt conditions. This downregulation of copper import in combination with high fructose consumption could have a synergist effect increasing the levels of oxidative stress (and therefore cellular damage) experienced by hepatocytes while lowering their ability to respond to it via superoxide dismutase. Using cell as well as animal models we aim to identify the mechanisms that allow oxidative stress, particularly that caused by diet, to regulate hepatic copper import and the systematic effects of this, as they related to NAFLD. These results could help explain the rising prevalence of NAFLD/NASH as well as identifying one potential mechanism that aids the progression of NAFLD to NASH.Support or Funding InformationInstitutional Development Award (IDeA)