Transcriptional regulation of fatty acid translocase/CD36 expression by CCAAT/enhancer-binding protein α

Abstract

Fatty acid translocase (FAT/CD36) plays an important role in facilitating long chain fatty acid transport. FAT/CD36 gene deletion protects mice from high fat diet-induced obesity. In this study we have investigated the regulatory mechanism of FAT/CD36 expression at the transcription level. FAT/CD36 expression was activated during 3T3-L1 adipocyte differentiation, and FAT/CD36 protein levels were positively correlated with CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ. However, a negative correlation was detected between FAT/CD36 and C/EBPβ. Overexpression of C/EBPα or C/EBPβ increased FAT/CD36 mRNA and protein levels in several types of cells. Restoration of C/EBPα or C/EBPβ expression in C/EBPα- or C/EBPβ-deficient mouse embryonic fibroblasts increased FAT/CD36 expression. However, in mouse embryonic fibroblasts C/EBPα was a more potent activator of FAT/CD36 expression than was C/EBPβ. Expression of C/EBPα robustly increased FAT/CD36 proximal promoter-directed luciferase expression in human embryonic kidney 293 cells. A C/EBP-responsive element was identified in the FAT/CD36 promoter by using 5′ and specific site mutations. The binding of C/EBPα in the FAT/CD36 promoter was detected by chromatin immunoprecipitation in 3T3-L1 adipocytes. These results demonstrated that C/EBPα regulates FAT/CD36 gene expression at the transcriptional level.