Transcriptional regulation of adipogenin expression in liver steatosis by hepatic peroxisome proliferator‐activated receptor gamma

The nuclear receptors peroxisome proliferator‐activated receptor gamma (PPARγ) and adipogenin (ADIG) play vital roles in lipid metabolism. However, the interaction between PPARγ and ADIG during liver steatosis remains unclear. In this study, we aimed to investigate the role of PPARγ in the transcriptional regulation of hepatic ADIG expression. Adig was found to be highly expressed in various fatty liver mouse models. Although hepatic Adig was expressed at high levels in the fatty liver of type 2 diabetic ob/ob mice and was upregulated by PPARγ agonist treatment, it was expressed at significantly low levels in liver‐specific Pparg‐knockout mice. Moreover, hepatic Adig expression was observed in other mouse models of liver steatosis, such as the leptin receptor mutant db/db and alcohol‐fed mice. Adig was also highly expressed in the white and brown adipose tissues, skeletal muscles, and heart of ob/ob mice. Reporter and electromobility shift assays showed that PPARγ positively regulates Adig transcriptional activity by directly binding to a functional PPARγ‐responsive element in the promoter region. Our results indicate that Adig is a novel target gene of hepatic PPARγ in liver steatosis. Adig is highly expressed in the fatty liver of ob/ob and other mice models. ADIG expression is reduced upon liver‐specific PPARγ knockout in ob/ob mice. PPARγ enhances Adig transcription by binding to the PPARγ‐responsive element.