CCAAT/Enhancer Binding Protein and Nuclear Factor-Y Regulate Adiponectin Gene Expression in Adipose Tissue

  1. Sang-kyu Park12,
  2. So-Young Oh12,
  3. Min-Young Lee12,
  4. Sarah Yoon12,
  5. Kyung-Sup Kim123 and
  6. Jae-woo Kim1
  1. 1Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Seoul, Korea
  2. 2Brain Korea 21 Project for Medical Science, Seoul, Korea
  3. 3Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, Seoul, Korea
  1. Address correspondence and reprint requests to Jae-woo Kim, MD, PhD, Department of BiochemistryMolecular Biology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-752, Korea. E-mail: japol13{at}yumc.yonsei.ac.kr

Abstract

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.

Footnotes

    • Accepted July 21, 2004.
    • Received April 2, 2004.
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