体育锻炼可降低循环脂多糖和 TLR4 激活，并改善 DIO 大鼠组织中的胰岛素信号转导。

OBJECTIVE

Insulin resistance in diet-induced obesity (DIO) is associated with a chronic systemic low-grade inflammation, and Toll-like receptor 4 (TLR4) plays an important role in the link among insulin resistance, inflammation, and obesity. The current study aimed to analyze the effect of exercise on TLR4 expression and activation in obese rats and its consequences on insulin sensitivity and signaling.

RESEARCH DESIGN AND METHODS

The effect of chronic and acute exercise was investigated on insulin sensitivity, insulin signaling, TLR4 activation, c-Jun NH(2)-terminal kinase (JNK) and IκB kinase (IKKβ) activity, and lipopolysaccharide (LPS) serum levels in tissues of DIO rats.

RESULTS

The results showed that chronic exercise reduced TLR4 mRNA and protein expression in liver, muscle, and adipose tissue. However, both acute and chronic exercise blunted TLR4 signaling in these tissues, including a reduction in JNK and IKKβ phosphorylation and IRS-1 serine 307 phosphorylation, and, in parallel, improved insulin-induced IR, IRS-1 tyrosine phosphorylation, and Akt serine phosphorylation, and reduced LPS serum levels.

CONCLUSIONS

Our results show that physical exercise in DIO rats, both acute and chronic, induces an important suppression in the TLR4 signaling pathway in the liver, muscle, and adipose tissue, reduces LPS serum levels, and improves insulin signaling and sensitivity. These data provide considerable progress in our understanding of the molecular events that link physical exercise to an improvement in inflammation and insulin resistance.

目的

饮食诱导肥胖（DIO）中的胰岛素抵抗与慢性全身性低度炎症有关，而 Toll 样受体 4（TLR4）在胰岛素抵抗、炎症和肥胖之间的联系中起着重要作用。本研究旨在分析运动对肥胖大鼠 TLR4 表达和激活的影响及其对胰岛素敏感性和信号转导的影响。

研究设计和方法

研究了慢性和急性运动对 DIO 大鼠胰岛素敏感性、胰岛素信号转导、TLR4 激活、c-Jun NH2-末端激酶（JNK）和 IκB 激酶（IKKβ）活性以及组织中脂多糖（LPS）血清水平的影响。

结果

结果表明，慢性运动可降低肝脏、肌肉和脂肪组织中 TLR4 mRNA 和蛋白表达。然而，急性和慢性运动均使这些组织中的 TLR4 信号转导减弱，包括 JNK 和 IKKβ磷酸化以及 IRS-1 丝氨酸 307 磷酸化减少，同时改善了胰岛素诱导的 IR、IRS-1 酪氨酸磷酸化和 Akt 丝氨酸磷酸化，并降低了 LPS 血清水平。