title: Concise Review: Current Status and Future Directions on Research Related to Nonalcoholic Fatty Liver Disease.
abstract: Considered a feature of the metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), is associated with insulin resistance, type 2 diabetes, obesity and drug toxicity. Its prevalence is estimated at about 30% in western countries mainly due to sedentary life styles and high fat diets. Genome-wide association studies have identified polymorphisms in several genes, for example, PNPLA3, and TM6SF2 which confer susceptibility to NAFLD. Here, we review recent findings in the NAFLD field with a particular focus on published transcriptomics datasets which we subject to a meta-analysis. We reveal a common gene signature correlating with the progression of the disease from steatosis and steatohepatitis and reveal that lipogenic and cholesterol metabolic pathways are main actors in this signature. We propose the use of disease-in-a-dish models based on hepatocyte-like cells derived from patient-specific induced pluripotent stem cells (iPSC). These will enable investigations into the contribution of genetic background in the progression from NALFD to non-alcoholic steatohepatitis. Furthermore, an iPSC-based approach should aid in the elucidation of the function of new biomarkers, thus enabling better diagnostic tests and validation of potential drug targets. Stem Cells 2017;35:89-96.
authors.affiliation: Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Wasco
authors.initials: W
authors.lastname: Wruck
authors.affiliation: Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Nina
authors.initials: N
authors.lastname: Graffmann
authors.affiliation: Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Marie-Ann
authors.initials: MA
authors.lastname: Kawala
authors.affiliation: Medical Faculty, Institute for Stem Cell Research and Regenerative Medicine, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: James
authors.initials: J
authors.lastname: Adjaye
mesh_terms: D000818:Animals; D035843:Biomedical Research; D018450:Disease Progression; D044127:Epigenesis, Genetic; D000069196:Gastrointestinal Microbiome; D055106:Genome-Wide Association Study; D006801:Humans; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*
keywords: Induced pluripotent stem cells; Meta-analysis; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Steatosis; microRNA