C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet
C3H/HeJ mice carrying a toll-like receptor 4 mutation are protected against the development of insulin resistance in white adipose tissue in response to a high-fat diet
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DOI：
10.1007/s00125-007-0654-8
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发表时间：
2007-06-01
期刊：
影响因子：
8.2
通讯作者：
Alessi, M. C.
中科院分区：
文献类型：
--
作者：
Poggi, M.;Bastelica, D.;Alessi, M. C.
目的/假设炎症与肥胖有关，并与糖尿病和动脉粥样硬化的发展有关。在革兰氏阴性细菌感染过程中，脂多糖通过toll样受体4 （TLR4）引起炎症反应，TLR4在诱导先天免疫和适应性免疫中具有重要作用。我们的目的是确定TLR4在高脂肪喂养期间代谢表型的发展中所起的作用。材料和方法我们评估了高脂肪饮食对TLR4突变小鼠（C3H/HeJ）及其对照的代谢影响。结果TLR4失活后，大鼠食量减少，体重无明显变化，但附睾脂肪组织质量增加，脂肪细胞肥大。它还能减轻炎症反应，增加葡萄糖转运，以及白色脂肪组织中脂联素和脂肪生成标志物的表达水平。此外，TLR4失活可减弱分化脂肪细胞中脂多糖诱导的胰岛素抵抗。TLR4突变小鼠摄食效率的提高与褐色脂肪组织质量降低和解偶联蛋白1基因表达降低有关。最后，TLR4失活减缓了肝脂肪变性的发展，降低了肝脏甘油三酯含量以及脂肪生成和纤维化标志物的表达水平。结论/解释TLR4影响白色脂肪组织炎症和胰岛素敏感性，以及肝脏脂肪储存，并在脂肪富集饮食期间的代谢表型调节中发挥重要作用。
Aims/hypothesis Inflammation is associated with obesity and has been implicated in the development of diabetes and atherosclerosis. During gram-negative bacterial infection, lipopolysaccharide causes an inflammatory reaction via toll-like receptor 4 (TLR4), which has an essential function in the induction of innate and adaptative immunity. Our aim was to determine what role TLR4 plays in the development of metabolic phenotypes during high-fat feeding.Materials and methods We evaluated metabolic consequences of a high-fat diet in TLR4 mutant mice (C3H/HeJ) and their respective controls.Results TLR4 inactivation reduced food intake without significant modification of body weight, but with higher epididymal adipose tissue mass and adipocyte hypertrophy. It also attenuated the inflammatory response and increased glucose transport and the expression levels of adiponectin and lipogenic markers in white adipose tissue. In addition, TLR4 inactivation blunted insulin resistance induced by lipopolysaccharide in differentiated adipocytes. Increased feeding efficiency in TLR4 mutant mice was associated with lower mass and lower expression of uncoupling protein 1 gene in brown adipose tissue. Finally, TLR4 inactivation slowed the development of hepatic steatosis, reducing the liver triacylglycerol content and also expression levels of lipogenic and fibrosis markers.Conclusions/interpretation TLR4 influences white adipose tissue inflammation and insulin sensitivity, as well as liver fat storage, and is important in the regulation of metabolic phenotype during a fat-enriched diet.