CCAAT/enhancer binding protein and nuclear factor-Y regulate adiponectin gene expression in adipose tissue.
Adiponectin is one of the adipokines secreted by adipocytes and regulates energy homeostasis associated with insulin sensitivity, suggesting a possibility of nutritional regulation of adiponectin gene expression. In this study, we showed that the transcription of adiponectin gene was induced 4-6 h after refeeding of mice. Also, differentiated 3T3-L1 adipocytes that were treated with high glucose expressed significantly increased adiponectin mRNA. Promoter analysis using nuclear extracts from white adipose tissue revealed that CCAAT/enhancer binding protein (C/EBP) and nuclear factor-Y (NF-Y) bound on the -117/-73 region of the adiponectin promoter. This region was critical for the activity of the adiponectin promoter as the deletion or mutation of this region markedly diminished the promoter activity to a basal level. Furthermore, the C/EBP binding increased in both refed animal and high glucose-treated 3T3-L1 adipocytes in an electrophoretic mobility shift assay, suggesting that C/EBP is responsible for the dietary response of the adiponectin gene expression. Chromatin immunoprecipitation studies demonstrated the binding of C/EBP and NF-Y in both mouse and differentiated 3T3-L1 adipocytes and also that C/EBP binding increased in response to high glucose. These findings demonstrated that C/EBP and NF-Y are critical for the regulation of the adiponectin expression in response to nutrients and in the course of adipocyte differentiation.
Park
Sang-kyu
SK
Department of BiochemistryMolecular Biology, Institute of Genetic Science, Seoul, Korea.
Oh
So-Young
SY
Lee
Min-Young
MY
Yoon
Sarah
S
Kim
Kyung-Sup
KS
Kim
Jae-woo
JW
D017667:Adipocytes / Q000166:cytology / Q000502:physiology*; D052242:Adiponectin; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D023081:CCAAT-Binding Factor / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000235:genetics / Q000502:physiology; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*
D052242:Adiponectin; D023081:CCAAT-Binding Factor; D022762:CCAAT-Enhancer-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C402244:nuclear factor Y; D003850:Deoxyribonuclease I