@article{4d41abd095964834aafebf6af1d79c8d,
title = "Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice",
abstract = "The gut microbiota plays a key role in host metabolism. Toll-like receptor 5 (TLR5), a flagellin receptor, is required for gut microbiota homeostasis. Accordingly, TLR5-deficient (T5KO) mice are prone to develop microbiota-dependent metabolic syndrome. Here we observed that T5KO mice display elevated neutral lipids with a compositional increase of oleate [C18:1 (n9)] relative to wild-type littermates. Increased oleate contribution to hepatic lipids and liver SCD1 expression were both microbiota dependent. Analysis of short-chain fatty acids (SCFAs) and 13C-acetate label incorporation revealed elevated SCFA in ceca and hepatic portal blood and increased liver de novo lipogenesis in T5KO mice. Dietary SCFAs further aggravated metabolic syndrome in T5KO mice. Deletion of hepatic SCD1 not only prevented hepatic neutral lipid oleate enrichment but also ameliorated metabolic syndrome in T5KO mice. Collectively, these results underscore the key role of the gut microbiota-liver axis in the pathogenesis of metabolic diseases.",
keywords = "Toll-like receptor 5, gut bacteria, hepatic neutral lipids, low-grade inflammation, metabolic diseases, monounsaturated fatty acids, short-chain fatty acids",
author = "Vishal Singh and Benoit Chassaing and Limin Zhang and {San Yeoh}, Beng and Xia Xiao and Manish Kumar and Baker, {Mark T.} and Jingwei Cai and Rachel Walker and Kamil Borkowski and Harvatine, {Kevin J.} and Nagendra Singh and Shearer, {Gregory C.} and Ntambi, {James M.} and Bina Joe and Patterson, {Andrew D.} and Gewirtz, {Andrew T.} and Matam Vijay-Kumar",
note = "Funding Information: M.V.-K. is supported by NIH grants K01, (DK083275), R03 (DK094864), and R01 (DK097865-01A1); A.T.G. by DK061417 and DK083890; and B.C. by Crohn{\textquoteright}s and Colitis Foundation of America (CCFA) Research Fellowship award. B.S.Y. is supported by NIH grant T32AI07445. A.D.P. is supported by NIH grant ES022186 and grant with the Pennsylvania Department of Health using Tobacco CURE Funds. B.J. is supported by NIH grants R01HL11264 and R01HL020176. We thank the Mouse Metabolic Phenotyping Center (MMPC)/DTRC Lipid laboratory (DK59637), Vanderbilt University, Nashville, TN. We thank Philip Smith, Director, Penn State Metabolomics Core Facility. We thank Jesse Aitken, Gayathri Srinivasan, Alyssa Grube, Jackie Yun Ying, and Rodrigo Aguilera for technical assistance. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
doi = "10.1016/j.cmet.2015.09.028",
language = "English (US)",
volume = "22",
pages = "983--996",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "6",
}