Oxysterol-binding protein-like 3 is a novel target gene of peroxisome proliferator-activated receptor γ in fatty liver disease

Oxysterol-binding protein-like 3 (OSBPL3) plays a key role in the development of fatty liver disease. Herein, we found that OSBPL3 is highly expressed in the fatty liver of humans and mice. Although high expression of Osbpl3 was observed in the fatty liver of type 2 diabetic ob/ob mice, liver-specific Pparg knockout ameliorated this increase in these mice. Moreover, high hepatic Osbpl3 expression was observed in other mice models of fatty liver disease, such as leptin receptor-mutant db/db and alcohol-fed mice. Analysis of the human liver transcriptome data revealed that hepatic OSBPL3 expression is higher in patients with advanced non-alcoholic fatty liver disease (NAFLD) when compared to those with mild NAFLD. Reporter and electrophoretic mobility shift assays showed that PPAR gamma positively regulates Osbpl3 transcription by binding to the two functional PPAR gamma-responsive elements present in the 5' upstream region. Overall, our results indicate that Osbpl3 is a novel PPAR gamma target in the fatty liver.