Transcriptional regulation of fatty acid translocase/CD36 expression by CCAAT/enhancer-binding protein alpha.
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 alpha (C/EBPalpha) and peroxisome proliferator-activated receptor gamma. However, a negative correlation was detected between FAT/CD36 and C/EBPbeta. Overexpression of C/EBPalpha or C/EBPbeta increased FAT/CD36 mRNA and protein levels in several types of cells. Restoration of C/EBPalpha or C/EBPbeta expression in C/EBPalpha- or C/EBPbeta-deficient mouse embryonic fibroblasts increased FAT/CD36 expression. However, in mouse embryonic fibroblasts C/EBPalpha was a more potent activator of FAT/CD36 expression than was C/EBPbeta. Expression of C/EBPalpha 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/EBPalpha in the FAT/CD36 promoter was detected by chromatin immunoprecipitation in 3T3-L1 adipocytes. These results demonstrated that C/EBPalpha regulates FAT/CD36 gene expression at the transcriptional level.
Qiao
Liping
L
Graduate Center for Nutritional Sciences, University of Kentucky, 900 S. Limestone, Lexington, KY 40536, USA.
Zou
Chenhui
C
Shao
Peng
P
Schaack
Jerome
J
Johnson
Peter F
PF
Shao
Jianhua
J
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004032:Diet; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020218:Response Elements / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D018955:CD36 Antigens; D012333:RNA, Messenger