β-adrenoceptor agonists downregulate adiponectin, but upregulate adiponectin receptor 2 and tumor necrosis factor-α expression in adipocytes
β-adrenoceptor agonists downregulate adiponectin, but upregulate adiponectin receptor 2 and tumor necrosis factor-α expression in adipocytes
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DOI：
10.1016/j.ejphar.2007.05.005
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发表时间：
2007-08-13
影响因子：
5
通讯作者：
Kawakami, Yasushi
中科院分区：
文献类型：
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作者：
Fu, Ling;Isobe, Kazumasa;Kawakami, Yasushi
最近，胰岛素致敏脂肪因子脂联素和胰岛素抵抗诱导脂肪因子肿瘤坏死因子- α (tnf - α)在脂肪细胞中相互抑制产生。我们研究了两种β(3)-肾上腺素受体激动剂5-[(2R)-2-[[(2R)-2-（3-氯苯基）-2-羟乙基]氨基]丙基]-1,3-苯二酚-2,2-二羧酸酯（CL-316,243）和(+/-)-(R*,R*)-[4-[2-[[2-（3-氯苯基）-2-羟乙基]氨基]丙基]苯氧基]乙酸（BRL37344）对C57BL/6J小鼠脂肪组织中脂联素、两种脂联素受体和tnf - α基因表达的影响。CL-316,243和BRL37344下调脂联素，但上调附睾或/和皮下白色脂肪组织和棕色脂肪组织中的脂联素受体2（非受体1）。tnf - α仅在附睾脂肪组织中表达上调。为了进一步探索这些影响，我们用非选择性β -肾上腺素能受体激动剂异丙肾上腺素治疗分化的3T3-L1脂肪细胞。因此，脂联素受体2（而非受体1）基因表达和tnf - α蛋白表达增加，但脂联素基因表达和分泌减少。异丙肾上腺素最可能通过β(2)、β(3)-肾上腺素受体、腺苷酸环化酶和蛋白激酶A （PKA）上调脂联素受体2。然而，伴随amp活化的蛋白激酶（AMPK）的激活可能抑制这种上调。我们的研究结果表明，β -肾上腺素受体激活导致的tnf - α上调和脂联素下调可能参与了儿茶酚胺诱导的胰岛素抵抗的发病机制，脂联素受体2的上调可能是脂联素减少的反馈结果。(c) 2007 Elsevier B.V.版权所有
Recently, the insulin-sensitizing adipokine adiponectin and the insulin resistance-inducing adipokine tumor necrosis factor-alpha (TNF-alpha) were reported to inhibit each other's production in adipocytes. We investigated the effects of two beta(3)-adrenoceptor agonists, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) and (+/-)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl] amino]propyl]phenoxy] acetic acid (BRL37344), on the gene expression of adiponectin, two adiponectin receptors, and TNF-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-alpha expression was upregulated only in epididymal adipose tissue. To further explore these effects, we treated differentiated 3T3-L1 adipocytes with the non-selective beta-adrenoceptor agonist isoproterenol. As a result, adiponectin receptor 2 (but not receptor 1) gene expression and TNF-alpha protein expression increased, but gene expression and secretion of adiponectin decreased. The upregulation of adiponectin receptor 2 by isoproterenol is most likely via beta(2),beta(3)-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-alpha and downregulation of adiponectin by beta-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. (c) 2007 Elsevier B.V. All rights reserved.