Systems biology approaches for studying the pathogenesis of non-alcoholic fatty liver disease.
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.
Ciarán P Fisher, Andrzej M Kierzek, Nick J Plant, J Bernadette Moore, Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, Surrey, United Kingdom.
Ciarán P
CP
Fisher
Ciarán P Fisher, Andrzej M Kierzek, Nick J Plant, J Bernadette Moore, Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, Surrey, United Kingdom.
Andrzej M
AM
Kierzek
Ciarán P Fisher, Andrzej M Kierzek, Nick J Plant, J Bernadette Moore, Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, Surrey, United Kingdom.
Nick J
NJ
Plant
Ciarán P Fisher, Andrzej M Kierzek, Nick J Plant, J Bernadette Moore, Faculty of Health and Medical Sciences, University of Surrey, GU2 7XH Guildford, Surrey, United Kingdom.
J Bernadette
JB
Moore
D000818:Animals; D003198:Computer Simulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D065626:Non-alcoholic Fatty Liver Disease / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D049490:Systems Biology
Metabolism; Modelling; Network; Non-alcoholic fatty liver disease; Regulation; Simulation; Systems biology