β-adrenoceptor agonists downregulate adiponectin, but upregulate adiponectin receptor 2 and tumor necrosis factor-greek small letter alpha expression in adipocytes

Autor: Fu, Ling, Isobe, Kazumasa, Zeng, Qin, Suzukawa, Kazumi, Takekoshi, Kazuhiro, Kawakami, Yasushi
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Zdroj: European journal of pharmacology. 569(1-2):155-162
ISSN: 0014-2999
Popis: application/pdf
Recently, the insulin-sensitizing adipokine adiponectin and the insulin resistance-inducing adipokine tumor necrosis factor-greek small letter alpha (TNF-greek small letter alpha) were reported to inhibit each other's production in adipocytes. We investigated the effects of two β3-adrenoceptor agonists, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) and (±)-(Rlow asterisk,Rlow asterisk)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid (BRL37344), on the gene expression of adiponectin, two adiponectin receptors, and TNF-greek small letter alpha in adipose tissues of C57BL/6J mice. CL-316,243 and BRL37344 downregulated adiponectin, but upregulated adiponectin receptor 2 (not receptor 1) in epididymal or/and subcutaneous white adipose tissues and in brown adipose tissue. TNF-greek small letter alpha expression was upregulated only in epididymal adipose tissue. To further explore these effects, we treated differentiated 3T3-L1 adipocytes with the non-selective β-adrenoceptor agonist isoproterenol. As a result, adiponectin receptor 2 (but not receptor 1) gene expression and TNF-greek small letter alpha protein expression increased, but gene expression and secretion of adiponectin decreased. The upregulation of adiponectin receptor 2 by isoproterenol is most likely via β2,β3-adrenoceptors, adenylyl cyclases, and protein kinase A (PKA). However, the accompanying activation of AMP-activated protein kinase (AMPK) may inhibit this upregulation. Our results suggest that upregulation of TNF-greek small letter alpha and downregulation of adiponectin by β-adrenoceptor activation may contribute to the pathogenesis of catecholamine-induced insulin resistance, and that upregulation of adiponectin receptor 2 may be a feedback result of reduced adiponectin.
Databáze: OpenAIRE
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