Absence of Tlr2 protects against high-fat diet-induced inflammation and results in greater insulin-stimulated glucose transport in cultured adipocytes
Absence of Tlr2 protects against high-fat diet-induced inflammation and results in greater insulin-stimulated glucose transport in cultured adipocytes
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DOI：
10.1016/j.jnutbio.2009.12.008
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发表时间：
2011-02-01
影响因子：
5.6
通讯作者：
Spurlock, Michael E.
中科院分区：
文献类型：
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作者：
Davis, Jeremy E.;Braucher, Douglas R.;Spurlock, Michael E.
我们先前已经证明Toll样受体-4(TLR4)参与肥胖诱导的脂肪组织(AT)炎症。然而，人们对TLR2在这一过程中的作用知之甚少。为了确定这种受体在肥胖诱导的炎症中的作用，我们利用雄性TLR2(-/-)小鼠，这些小鼠回交到饮食诱导肥胖(DIO)的小鼠模型上。小鼠随机给予低脂对照组(LFD)或高脂饮食(HFD)16周。尽管体重或能量摄入量的差异可以忽略不计。TLR2(-/-)小鼠不受高脂饲料诱导的肥胖的影响，这一点通过减少附睾脂垫重量和体脂含量得到了明显的证明。与这些效应相对应的是TLR2(-/-)小鼠AT中F4/80阳性巨噬细胞的钝性聚集。此外，TLR2(-/-)小鼠AT中单核细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(INF-α)和一氧化氮合酶-2(NOS2)等促炎介质的转录丰度对DIO的反应程度较低或较低。胰岛素敏感性的血清标记物没有显著差异(数据未显示)。然而，从TLR2(-/-)小鼠的AT分离的基质血管细胞(SVCs)的脂肪细胞比TLR2(+/+)小鼠的脂肪细胞有更多的基础和胰岛素刺激的葡萄糖摄取。此外，TLR2(-/-)的缺失排除了酵母多糖A(ZymA)诱导的胰岛素抵抗，但棕榈酸酯不能。这些数据表明，TLR2可能直接参与了HFD诱导的炎症反应，也可能调节脂肪细胞基础和胰岛素刺激的葡萄糖摄取。(C)2011 Elsevier Inc.保留所有权利。
We have previously shown that toll-like receptor-4 (Tlr4) is involved in obesity-induced inflammation in adipose tissue (AT). However, less is known about the role of Tlr2 in this process. To determine the involvement of this receptor in obesity-induced inflammation, we utilized male Tlr2(-/-) mice that were backcrossed onto a mouse model of diet-induced obesity (DIO). Mice were fed either low-fat control (LFD) or high-fat diet (HFD) ad libitum for 16 weeks. Despite negligible differences in body weight or energy intake. Tlr2(-/-) mice were protected from HFD-induced adiposity as was evident by reduced epididymal fat pad weight and carcass lipid content. Corresponding with these effects was a blunted accumulation of F4/80-positive macrophages in AT of Tlr2(-/-) mice. Furthermore, transcript abundance of proinflammatory mediators, including monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (INF alpha) and nitric oxide synthase-2 (NOS2) in AT of Tlr2(-/-) mice, was lower or less responsive to DIO. There were no significant differences in serum markers of insulin sensitivity (data not shown). However, adipocytes derived from stromal vascular cells (SVCs) isolated from AT of Tlr2(-/-) mice had considerably greater basal and insulin-stimulated glucose uptake as compared with those obtained from Tlr2(+/+) mice. Furthermore, the absence of Tlr2(-/-) precluded the induction of insulin resistance by zymosan A (ZymA) but not by palmitate. These data indicate that Tlr2 may be directly involved in HFD-induced inflammation and may also regulate basal and insulin-stimulated glucose uptake in adipocytes. (C) 2011 Elsevier Inc. All rights reserved.