Angiotensin receptor 1 blocker valsartan normalizes gene expression profiles of 3T3-L1 adipocytes altered by co-culture with LPS-treated RAW264.7 macrophages
Angiotensin receptor 1 blocker valsartan normalizes gene expression profiles of 3T3-L1 adipocytes altered by co-culture with LPS-treated RAW264.7 macrophages
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DOI：
10.1016/j.orcp.2012.05.005
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发表时间：
2012-10-01
影响因子：
4.3
通讯作者：
Asano, Tomoichiro
中科院分区：
文献类型：
--
作者：
Kumamoto, Sonoko;Kushiyama, Akifumi;Asano, Tomoichiro
据报道，脂肪组织中的巨噬细胞在与肥胖相关的胰岛素抵抗和慢性炎症的发展中起主要作用。另一方面，一些临床试验已经揭示了血管紧张素II受体阻滞剂（ARB），以改善胰岛素抵抗。在这项研究中，我们分析了3 T3-L1脂肪细胞与LPS处理的RAW 264. 7巨噬细胞在存在或不存在血管紧张素受体1阻断剂缬沙坦的情况下共培养4，8，12和24 h的基因表达谱。使用Key-Molnet Lite分析其表达受LPS处理的RAW巨噬细胞影响但通过共添加缬沙坦而标准化的基因。它们包括许多NF-κ B、甲状腺受体和AP-1靶转录物。此外，半胱天冬酶，整合素，基质金属肽酶和脂肪形成基因的表达模式，改变了与LPS处理的RAW细胞共培养，一般正常的缬沙坦治疗。根据这些数据，有理由认为缬沙坦可以使巨噬细胞浸润的脂肪组织中改变的基因表达模式正常化，并改善脂肪组织的炎症、凋亡和纤维化变化。尽管ARB可能通过多种机制改善胰岛素抵抗，例如，通过循环系统对肌肉或其他组织的影响，但这是第一份证明缬沙坦的有利作用涉及脂肪细胞和巨噬细胞之间相互作用的正常化的报告。缬沙坦的这种作用机制为开发肥胖相关胰岛素抵抗的治疗方法提供了希望。(C)2012年由爱思唯尔有限公司代表亚洲大洋洲肥胖研究协会发布。
Macrophages in adipose tissue reportedly play a major role in the development of insulin resistance and chronic inflammation associated with obesity. On the other hand, several clinical trials have revealed angiotensin II receptor blockers (ARBs) to improve insulin resistance. In this study, we analyzed the gene expression profile of 3T3-L1 adipocytes co-cultured with LPS-treated RAW264.7 macrophages in the presence or the absence of the angiotensin receptor 1 blocker valsartan, for 4, 8, 12 and 24 h. The genes of which expressions were affected by LPS-treated RAW macrophages but normalized by co-addition of valsartan were analyzed using Key-Molnet Lite. They included many NF-kappa B, thyroid receptor and AP-1 target transcripts. In addition, the expression patterns of caspases, integrins, matrix metallopeptidases and adipogenic genes, altered by co-culture with LPS-treated RAW cells, were generally normalized by valsartan treatment. In light of these data, it is reasonable to consider valsartan to normalize altered gene expression patterns in adipose tissue infiltrated by macrophages, and to ameliorate inflammation, apoptosis and fibrotic changes of adipose tissue. Although there may be multiple mechanisms by which ARBs ameliorate insulin resistance, for example, through effects on muscle or other tissues via the circulatory system, this is the first report demonstrating that a favorable effect of valsartan involves normalization of the interaction between adipocytes and macrophages. This mechanism of valsartan action holds promise for developing treatments for obesity-related insulin resistance. (C) 2012 Published by Elsevier Ltd on behalf of Asian Oceanian Association for the Study of Obesity.