Adipogenin Is A Novel Target Gene for CCAAT/Enhancer-Binding Protein α

Adipogenin (Adig) is a lipid droplet-associated protein that promotes lipid droplet growth. CCAAT/enhancer-binding protein α (C/EBPα) is a transcription factor enriched in white adipose tissue and liver and is a key regulator of hepatic gene expression. In this study, we investigated the molecular mechanism by which C/EBPα regulates Adig gene expression in the liver of type 2 diabetic model (ob/ob) mice. Although hepatic C/EBPα expression levels were comparable between control and ob/ob mice, both Adig mRNA levels and the putative ADIG signal were significantly elevated in the fatty liver of ob/ob mice. This induction of Adig was markedly repressed by liver-specific C/EBPα deficiency. Analysis of publicly available chromatin immunoprecipitation sequencing (ChIP-seq) data revealed a C/EBPα-binding peak within the Adig promoter region in the mouse liver. Within this peak, we identified a putative C/EBP response element (Adig-CEBPRE, located at positions -87 to -79) that was relatively well conserved across multiple species, suggesting an evolutionarily conserved role of C/EBPα in Adig regulation. Reporter assays demonstrated that luciferase activity driven by Adig-CEBPRE was significantly induced by either C/EBPα or C/EBPβ, whereas this induction was abolished upon deletion of Adig-CEBPRE. Collectively, these findings indicate that Adig is a novel C/EBPα target gene in the steatotic liver of ob/ob mice, providing a mechanistic link between hepatic transcriptional regulation and lipid droplet homeostasis.