Published online Nov 7, 2014. doi: 10.3748/wjg.v20.i41.15070
Revised: February 13, 2014
Accepted: March 12, 2014
Published online: November 7, 2014
Non-alcoholic fatty liver disease (NAFLD) is a progressive disease of increasing public health concern. In western populations the disease has an estimated prevalence of 20%-40%, rising to 70%-90% in obese and type II diabetic individuals. Simplistically, NAFLD is the macroscopic accumulation of lipid in the liver, and is viewed as the hepatic manifestation of the metabolic syndrome. However, the molecular mechanisms mediating both the initial development of steatosis and its progression through non-alcoholic steatohepatitis to debilitating and potentially fatal fibrosis and cirrhosis are only partially understood. Despite increased research in this field, the development of non-invasive clinical diagnostic tools and the discovery of novel therapeutic targets has been frustratingly slow. We note that, to date, NAFLD research has been dominated by in vivo experiments in animal models and human clinical studies. Systems biology tools and novel computational simulation techniques allow the study of large-scale metabolic networks and the impact of their dysregulation on health. Here we review current systems biology tools and discuss the benefits to their application to the study of NAFLD. We propose that a systems approach utilising novel in silico modelling and simulation techniques is key to a more comprehensive, better targeted NAFLD research strategy. Such an approach will accelerate the progress of research and vital translation into clinic.
Core tip: Research into non-alcoholic fatty liver disease (NAFLD) is dominated by human clinical studies and the use of animal models. We postulate that the wider use of systems biology approaches, incorporating novel modelling and simulation strategies, will yield greater insights into the mechanisms underlying NAFLD progression. Such insights are essential to the development of non-invasive diagnostic tools and novel therapies.