Danio rerio Transcriptome or Gene expression

Inflammation is a constant companion of Non-Alcoholic Fatty Liver Disease (NAFLD). However, it is generally considered to be a consequence rather than cause. Using a transgenic model we demonstrate that chronic systemic exposure to human IL6 causes intrahepatic triglyceride accumulation in the zebrafish. The inflammation based zebrafish model for NAFLD has a transcriptome signature distinct from the diet based NAFLD models. Instead, a marked deregulation of glycolysis/gluconeogenesis pathway, specifically a robust down regulation of the glycolytic enzyme aldolase b, was evident in both transcriptomics and proteomics studies of liver exposed to IL6. Metabolomics of the zebrafish liver showed accumulation of hexose monophosphates. This is reminiscent of patients of the genetic disease Hereditary Fructose Intolerance (HFI) caused by aldolase B deficiency and HFI patients appear to have a higher propensity to develop fatty liver disease than controls.In Caucasians NAFLD is generally associated with obesity. However, in the South Asian population, lean males have been noted to develop NAFLD. Asian-Indians also seem to have higher basal circulating IL6. Our inflammation-based zebrafish transgenic might model this emerging category of NAFLD better than the conventional high fat diet based NAFLD animal models. Our study suggests that inflammation driven repression of aldolase b may be a novel mechanism for accumulation of intrahepatic triglyceride, especially in obesity independent NAFLD.