Modeling Nonalcoholic Fatty Liver Disease with Human Pluripotent Stem Cell-Derived Immature Hepatocyte-Like Cells Reveals Activation of PLIN2 and Confirms Regulatory Functions of Peroxisome Proliferator-Activated Receptor Alpha.

ABSTRACT: Nonalcoholic fatty liver disease (NAFLD/steatosis) is a metabolic disease characterized by the incorporation of fat into hepatocytes. In this study, we developed an in vitro model for NAFLD based on hepatocyte-like cells (HLCs) differentiated from human pluripotent stem cells. We induced fat storage in these HLCs and detected major expression changes of metabolism-associated genes, as well as an overall reduction of liver-related microRNAs. We observed an upregulation of the lipid droplet coating protein Perilipin 2 (PLIN2), as well as of numerous genes of the peroxisome proliferator-activated receptor (PPAR) pathway, which constitutes a regulatory hub for metabolic processes. Interference with PLIN2 and PPARα resulted in major alterations in gene expression, especially affecting lipid, gl

SUBMITTER: Graffmann N 

PROVIDER: S-EPMC4971413 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature