Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2.
Receptor for advanced glycation end products regulates adipocyte hypertrophy and insulin sensitivity in mice: involvement of Toll-like receptor 2.
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作者：
Monden M;Koyama H;Otsuka Y;Morioka T;Mori K;Shoji T;Mima Y;Motoyama K;Fukumoto S;Shioi A;Emoto M;Yamamoto Y;Yamamoto H;Nishizawa Y;Kurajoh M;Yamamoto T;Inaba M
晚期糖基化终末产物 (RAGE) 受体已被证明与肥胖和动脉粥样硬化有关，即使在非糖尿病情况下也是如此。在这项研究中，我们研究了 RAGE 如何调节肥胖和胰岛素敏感性的潜在机制。使用腺病毒基因转移在3T3-L1前脂肪细胞中过度表达RAGE会加速脂肪细胞肥大，而小干扰RNA抑制RAGE则显着减少脂肪细胞肥大。此外，高迁移率族box-1和S100b（两者都是在3T3-L1细胞中内源表达的RAGE配体）的双重敲低，也消除了RAGE介导的脂肪细胞肥大，暗示配体的基本作用——RAGE连接。 RAGE 过表达诱导的脂肪细胞肥大与 4 型葡萄糖转运蛋白和脂联素 mRNA 表达的抑制、胰岛素刺激的葡萄糖摄取和胰岛素刺激的信号传导减弱有关。 Toll 样受体 (Tlr)2 mRNA（而非 Tlr4 mRNA）会因 RAGE 过度表达而迅速上调，抑制 Tlr2 几乎完全消除 RAGE 介导的脂肪细胞肥大。最后，与野生型小鼠相比，RAGE−/− 小鼠的体重、附睾脂肪重量、附睾脂肪细胞大小、血清脂联素水平和胰岛素敏感性均显着降低。 RAGE 缺陷与脂肪组织中 Tlr2 mRNA 表达的早期抑制有关。因此，RAGE 似乎与小鼠脂肪细胞肥大和胰岛素敏感性有关，而 Tlr2 调节可能发挥了部分作用。
Receptor for advanced glycation end products (RAGE) has been shown to be involved in adiposity as well as atherosclerosis even in nondiabetic conditions. In this study, we examined mechanisms underlying how RAGE regulates adiposity and insulin sensitivity. RAGE overexpression in 3T3-L1 preadipocytes using adenoviral gene transfer accelerated adipocyte hypertrophy, whereas inhibitions of RAGE by small interfering RNA significantly decrease adipocyte hypertrophy. Furthermore, double knockdown of high mobility group box-1 and S100b, both of which are RAGE ligands endogenously expressed in 3T3-L1 cells, also canceled RAGE-medicated adipocyte hypertrophy, implicating a fundamental role of ligands–RAGE ligation. Adipocyte hypertrophy induced by RAGE overexpression is associated with suppression of glucose transporter type 4 and adiponectin mRNA expression, attenuated insulin-stimulated glucose uptake, and insulin-stimulated signaling. Toll-like receptor (Tlr)2 mRNA, but not Tlr4 mRNA, is rapidly upregulated by RAGE overexpression, and inhibition of Tlr2 almost completely abrogates RAGE-mediated adipocyte hypertrophy. Finally, RAGE−/− mice exhibited significantly less body weight, epididymal fat weight, epididymal adipocyte size, higher serum adiponectin levels, and higher insulin sensitivity than wild-type mice. RAGE deficiency is associated with early suppression of Tlr2 mRNA expression in adipose tissues. Thus, RAGE appears to be involved in mouse adipocyte hypertrophy and insulin sensitivity, whereas Tlr2 regulation may partly play a role.
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影响因子：
4.8
作者：
Braga, Carla W.;Martinez, Denis;Souza, Diogo Onofre
通讯作者：
Souza, Diogo Onofre
影响因子：
15.9
作者：
Harja, Evis;Bu, De-Xiu;Schmidt, Ann Marie
通讯作者：
Schmidt, Ann Marie
影响因子：
5.6
作者：
Davis, Jeremy E.;Braucher, Douglas R.;Spurlock, Michael E.
通讯作者：
Spurlock, Michael E.
DOI：
10.1161/atvbaha.110.210427
发表时间：
2010-11
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Abe Y;Kawakami A;Osaka M;Uematsu S;Akira S;Shimokado K;Sacks FM;Yoshida M
通讯作者：
Yoshida M
影响因子：
6.5
作者：
Lee, YH;Chen, SY;Huang, YF
通讯作者：
Huang, YF