1. Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice
- Author
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Gregory C. Shearer, Nagendra Singh, Vishal Singh, Benoit Chassaing, Limin Zhang, Rachel E Walker, Jingwei Cai, Kamil Borkowski, James M. Ntambi, Manish Kumar, Andrew T. Gewirtz, Beng San Yeoh, Mark T. Baker, Bina Joe, Matam Vijay-Kumar, Andrew D. Patterson, Xia Xiao, and Kevin J. Harvatine
- Subjects
Male ,Magnetic Resonance Spectroscopy ,Physiology ,030204 cardiovascular system & hematology ,Gut flora ,metabolic diseases ,Feces ,Mice ,0302 clinical medicine ,fluids and secretions ,low-grade inflammation ,Metabolic Syndrome ,Mice, Knockout ,0303 health sciences ,Microbiota ,monounsaturated fatty acids ,Up-Regulation ,3. Good health ,Intestines ,Liver ,Lipogenesis ,Female ,lipids (amino acids, peptides, and proteins) ,hepatic neutral lipids ,Stearoyl-CoA Desaturase ,gut bacteria ,medicine.medical_specialty ,short-chain fatty acids ,Biology ,Diet, High-Fat ,digestive system ,03 medical and health sciences ,Insulin resistance ,Internal medicine ,medicine ,Animals ,Molecular Biology ,Caloric Restriction ,030304 developmental biology ,Body Weight ,Metabolism ,Cell Biology ,Fatty Acids, Volatile ,biology.organism_classification ,medicine.disease ,Toll-like receptor 5 ,stomatognathic diseases ,Endocrinology ,TLR5 ,Insulin Resistance ,Metabolic syndrome ,Stearoyl-CoA desaturase-1 ,Homeostasis ,Oleic Acid - Abstract
SummaryThe 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.
- Published
- 2015
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