Systems biology approaches for studying the pathogenesis of non-alcoholic fatty liver disease

Abstract

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.

Keywords: Metabolism; Modelling; Network; Non-alcoholic fatty liver disease; Regulation; Simulation; Systems biology.

Figure 1

Progression and stages of non-alcoholic fatty liver disease. Livers, representing macroscopic changes with inserted micrographs of histological sections; collagen fibres stained with Masson’s trichrome stain (blue). Arrows represent disease progression/regression (dashed).

Figure 2

Non-alcoholic fatty liver disease publications and distribution of research. Graph shows the number of journal articles published (as listed on PubMed) between 2002 and 2012 focused on non-alcoholic fatty liver disease; pie chart shows the distribution of models/approaches (human, in vivo, in vitro, systems approach) used in research published during 2012.