Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.
Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.
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DOI：
10.1126/science.1179721
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发表时间：
2010-04-09
期刊：
影响因子：
--
通讯作者：
Gewirtz AT
中科院分区：
文献类型：
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作者：
Vijay-Kumar M;Aitken JD;Carvalho FA;Cullender TC;Mwangi S;Srinivasan S;Sitaraman SV;Knight R;Ley RE;Gewirtz AT
代谢综合征是一组肥胖相关的代谢异常，增加了个体发展为2型糖尿病和心血管疾病的风险。在这里，我们表明，小鼠Toll样受体5（TLR5），先天免疫系统的一个组成部分，在肠道粘膜中表达，并有助于抵御感染，表现出暴食症和发展代谢综合征的标志性特征，包括高脂血症，高血压，胰岛素抵抗和肥胖增加的基因缺陷。这些代谢变化与肠道微生物群组成的变化相关，并且肠道微生物群从TLR5缺陷小鼠转移到野生型无菌小鼠赋予受体代谢综合征的许多特征。在TLR5缺陷的小鼠中，食物限制可以预防肥胖，但不能预防胰岛素抵抗。这些结果支持了肠道微生物群导致代谢疾病的新观点，并表明先天免疫系统的功能障碍可能会促进代谢综合征的发展。
Metabolic syndrome is a group of obesity-related metabolic abnormalities that increase an individual’s risk of developing type 2 diabetes and cardiovascular disease. Here, we show that mice genetically deficient in Toll-like receptor 5 (TLR5), a component of the innate immune system that is expressed in the gut mucosa and that helps defend against infection, exhibit hyperphagia and develop hallmark features of metabolic syndrome, including hyperlipidemia, hypertension, insulin resistance, and increased adiposity. These metabolic changes correlated with changes in the composition of the gut microbiota, and transfer of the gut microbiota from TLR5-deficient mice to wild-type germ-free mice conferred many features of metabolic syndrome to the recipients. Food restriction prevented obesity, but not insulin resistance, in the TLR5-deficient mice. These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome.