Involvement of toll-like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis.
Involvement of toll-like receptor 4 in alveolar bone loss and glucose homeostasis in experimental periodontitis.
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DOI：
10.1111/j.1600-0765.2010.01304.x
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发表时间：
2011-02
影响因子：
3.5
通讯作者：
Unterman TG
中科院分区：
文献类型：
--
作者：
Watanabe K;Iizuka T;Adeleke A;Pham L;Shlimon AE;Yasin M;Horvath P;Unterman TG
普遍认为某些脂肪酸和脂多糖（LPS）通过Toll样受体4（TLR 4）促进炎症，并且炎症促进胰岛素抵抗。因此，我们假设，与喂食高脂（HF）饮食的牙周炎野生型（WT）动物相比，喂食高脂饮食的牙周炎和TLR 4功能丧失（LOF）突变的小鼠将改善葡萄糖稳态。将喂食HF饮食的野生型和TLR 4突变小鼠分成四组（n = 6/组）：WT; WT伴牙周炎（WT/P）;突变体（Mut）;和突变伴牙周炎（Mut/P）。牙周炎通过将LPS浸泡的结扎线放置在上颌第二磨牙周围来诱导。每周测定空腹胰岛素和血糖水平，持续10周。在基线（第1周）和第9周评价葡萄糖耐量。第10周处死小鼠时，测定肝脏中胰岛素信号传导（Akt磷酸化）和肿瘤坏死因子-α（TNF-α）mRNA水平。与WT/P小鼠相比，Mut/P小鼠的牙槽骨丢失较少（p < 0.05）。与Mut、WT和WT/P小鼠相比，在喂食HF饮食8周（第9和10周）后，Mut/P小鼠的空腹葡萄糖水平得到改善（p < 0.05）。与基线相比，除Mut/P组外，所有组的葡萄糖耐量均受损（p < 0.05）。与WT/P小鼠相比，Mut/P小鼠肝脏中的胰岛素信号传导得到改善（p <0.05），并且TNF-α的表达降低（p < 0.05）。TLR 4 LOF突变可部分防止喂食HF饮食的牙周炎小鼠的牙槽骨丢失并改善葡萄糖稳态。
There is general agreement that certain fatty acids and lipopolysaccharides (LPS) promote inflammation through toll-like receptor 4 (TLR4), and that inflammation promotes insulin resistance. We therefore hypothesized that mice with periodontitis and a TLR4 loss-of-function (LOF) mutation fed a high-fat (HF) diet would develop improved glucose homeostasis compared with wild-type (WT) animals with periodontitis fed a HF diet. Wild-type and TLR4 mutant mice fed a HF diet were divided into four groups (n = 6/group): WT; WT with periodontitis (WT/P); mutant (Mut); and mutant with periodontitis (Mut/P). Periodontitis was induced by placing LPS soaked ligatures around maxillary second molars. Fasting insulin and glucose levels were measured weekly for 10 wk. Glucose tolerance was evaluated at baseline (week 1) and at 9 wk. Insulin signaling (phosphorylation of Akt) and tumor necrosis factor-α (TNF-α) mRNA levels in liver were determined when the mice were killed at week 10. Mut/P mice developed less alveolar bone loss compared with WT/P mice (p < 0.05). Fasting glucose levels were improved after 8 wk of feeding a HF diet (weeks 9 and 10) in Mut/P mice compared with Mut, WT and WT/P mice (p < 0.05). Glucose tolerance was impaired in all groups compared with baseline (p < 0.05), except for the Mut/P group. Insulin signaling was improved (p < 0.05), and expression of TNF-α was decreased (p < 0.05) in the liver of Mut/P mice compared with the liver of WT/P mice. The TLR4 LOF mutation partially protects against alveolar bone loss and improves glucose homeostasis in mice with periodontitis fed a HF diet.