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5‐Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue
Author(s) -
Uchida-Kitajima Shoko,
Yamauchi Toshimasa,
Takashina Youko,
Okada-Iwabu Miki,
Iwabu Masato,
Ueki Kohjiro,
Kadowaki Takashi
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.07.044
Subject(s) - adiponectin , receptor , medicine , endocrinology , adipose tissue , plasminogen activator inhibitor 1 , adiponectin receptor 1 , activator (genetics) , gene expression , chemistry , signal transduction , receptor expression , biology , microbiology and biotechnology , plasminogen activator , gene , insulin resistance , biochemistry , insulin
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‐HT 2A receptors was up‐regulated in hypertrophic 3T3‐L1 adipocytes, which exhibited decreased expression of adiponectin and increased expression of PAI‐1. 5‐HT 2A receptor antagonists and suppression of 5‐HT 2A 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‐HT 2A receptor blockade reduced PAI‐1 expression. These findings indicate that antagonism of 5‐HT 2A receptors in adipocytes could improve the obesity‐linked decreases in adiponectin expression and increases in PAI‐1 expression.