5-Hydroxytryptamine 2A receptor signaling cascade modulates adiponectin and plasminogen activator inhibitor 1 expression in adipose tissue.
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.
Uchida-Kitajima
Shoko
S
Pharmacology Department II, Mitsubishi Tanabe Pharma Corporation, Toda-shi, Saitama 335-8505, Japan.
Yamauchi
Toshimasa
T
Takashina
Youko
Y
Okada-Iwabu
Miki
M
Iwabu
Masato
M
Ueki
Kohjiro
K
Kadowaki
Takashi
T
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D052242:Adiponectin / Q000096:biosynthesis* / Q000235:genetics; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists; D015398:Signal Transduction
D052242:Adiponectin; D017395:Plasminogen Activator Inhibitor 1; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists