title: Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.
abstract: Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment.
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; email: joel.haas@pasteur-lille.fr , bart.staels@pasteur-lille.fr.|Université de Lille, F-59000 Lille, France.|INSERM UMR 1011, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Haas
authors.affiliation: Department of Gastroenterology and Hepatology, Antwerp University Hospital, 2650 Antwerp, Belgium; email: sven.francque@uza.be.|Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France; email: joel.haas@pasteur-lille.fr , bart.staels@pasteur-lille.fr.|Université de Lille, F-59000 Lille, France.|INSERM UMR 1011, F-59000 Lille, France.|Institut Pasteur de Lille, F-59000 Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000473:pathology; D024821:Metabolic Syndrome / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000473:pathology*; D009765:Obesity / Q000473:pathology; D012307:Risk Factors
keywords: cardiovascular disease; fibrosis; hepatocellular carcinoma; metabolic syndrome; obesity