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Transcription factor AP-2β inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes

International Journal of Obesity volume 34, pages 670–678 (2010)Cite this article

Subjects

Abstract

Background:

We have previously reported an association between the activator protein-2β (AP-2β) transcription factor gene and type 2 diabetes. This gene is preferentially expressed in adipose tissue, and subjects with a disease-susceptible allele of AP-2β showed stronger AP-2β expression in adipose tissue than those without the susceptible allele. Furthermore, overexpression of AP-2β led to lipid accumulation and induced insulin resistance in 3T3-L1 adipocytes.

Result:

We found that overexpression of AP-2β in 3T3-L1 adipocytes decreased the promoter activity of leptin, and subsequently decreased both messenger RNA (mRNA) and protein expression and secretion. Furthermore, knockdown of endogenous AP-2β by RNA-interference increased mRNA and protein expression of leptin. Electrophoretic mobility shift and chromatin immunoprecipitation assays revealed specific binding of AP-2β to leptin promoter regions in vitro and in vivo. In addition, site-directed mutagenesis of the AP-2-binding site located between position +34 and +42 relative to the transcription start site abolished the inhibitory effect of AP-2β. Our results clearly showed that AP-2β directly inhibited insulin-sensitizing hormone leptin expression by binding to its promoter.

Conclusion:

AP-2β modulated the expression of leptin through direct interaction with its promoter region.

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Acknowledgements

We thank JM Olefsky (University of California, San Diego, CA, USA) for providing 3T3-L1 adipocytes. We also thank Ms K Kosaka for excellent technical assistance. This study was supported in part by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to SU and HM).

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Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan

    T Fuke, T Yoshizaki, M Kondo, K Morino, T Obata, S Ugi, Y Nishio, A Kashiwagi & H Maegawa

  2. Center for Genomic Medicine, Laboratory for Endocrinology and Metabolism, Institute of Physical and Chemical Research, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, Japan

    S Maeda

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  1. T Fuke
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Correspondence to H Maegawa.

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Fuke, T., Yoshizaki, T., Kondo, M. et al. Transcription factor AP-2β inhibits expression and secretion of leptin, an insulin-sensitizing hormone, in 3T3-L1 adipocytes. Int J Obes 34, 670–678 (2010). https://doi.org/10.1038/ijo.2009.295

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