FEBS Letters
Volume 582, Issue 20 , Pages 3037-3044, 3 September 2008

5-Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue

Edited by Laszlo Nagy

  • Shoko Uchida-Kitajima

      Affiliations

    • Pharmacology Department II, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan
    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Toshimasa Yamauchi

      Affiliations

    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Youko Takashina

      Affiliations

    • Pharmacology Department II, Mitsubishi Tanabe Pharma Corporation, 2-2-50, Kawagishi, Toda-shi, Saitama 335-8505, Japan
    • ,
  • Miki Okada-Iwabu

      Affiliations

    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Masato Iwabu

      Affiliations

    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Kohjiro Ueki

      Affiliations

    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • ,
  • Takashi Kadowaki

      Affiliations

    • Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • Department of Integrated Molecular Science on Metabolic Diseases, 22nd Century Medical and Research Center, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan
    • Corresponding Author InformationCorresponding author. Address: Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Fax: +81 3 5800 9167.

Received 28 April 2008; received in revised form 4 July 2008; accepted 20 July 2008. published online 01 August 2008.

Abstract 

Knowledge of the regulatory factors associated with down-regulation of adiponectin gene expression and up-regulation of PAI-1 gene expression is crucial to understand the pathophysiological basis of obesity and metabolic diseases, and could establish new treatment strategies for these conditions. We showed that expression of 5-HT2A receptors was up-regulated in hypertrophic 3T3-L1 adipocytes, which exhibited decreased expression of adiponectin and increased expression of PAI-1. 5-HT2A receptor antagonists and suppression of 5-HT2A receptor gene expression enhanced adiponectin expression. Activation of Gq negatively regulated adiponectin expression, and inhibition of mitogen-activated protein kinase reversed the Gq-induced effect. Moreover, the 5-HT2A receptor blockade reduced PAI-1 expression. These findings indicate that antagonism of 5-HT2A receptors in adipocytes could improve the obesity-linked decreases in adiponectin expression and increases in PAI-1 expression.

Keywords: Adiponectin, Adipocytes, 5-HT2A receptor, Plasminogen activator inhibitor-1, Sarpogrelate

 

PII: S0014-5793(08)00645-5

doi:10.1016/j.febslet.2008.07.044

FEBS Letters
Volume 582, Issue 20 , Pages 3037-3044, 3 September 2008

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