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Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.


ABSTRACT: 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.

SUBMITTER: Vijay-Kumar M 

PROVIDER: S-EPMC4714868 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5.

Vijay-Kumar Matam M   Aitken Jesse D JD   Carvalho Frederic A FA   Cullender Tyler C TC   Mwangi Simon S   Srinivasan Shanthi S   Sitaraman Shanthi V SV   Knight Rob R   Ley Ruth E RE   Gewirtz Andrew T AT  

Science (New York, N.Y.) 20100304 5975


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 in  ...[more]

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