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 (13)C-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.
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Singh
authors.affiliation: Institute for Biomedical Sciences, Center for Inflammation, Immunity & Infection, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Benoit
authors.initials: B
authors.lastname: Chassaing
authors.affiliation: Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary & Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA; CAS & State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics & National Centre for Magnetic Resonance, Wuhan, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Beng
authors.initials: B
authors.lastname: San Yeoh
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Institute for Biomedical Sciences, Center for Inflammation, Immunity & Infection, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Baker
authors.affiliation: Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary & Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Walker
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Kamil
authors.initials: K
authors.lastname: Borkowski
authors.affiliation: Department of Animal Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harvatine
authors.affiliation: Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Nagendra
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Shearer
authors.affiliation: Department of Biochemistry and Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
authors.affiliation: Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Toledo, OH 43614, USA.
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.affiliation: Center for Molecular Toxicology and Carcinogenesis, Department of Veterinary & Biomedical Sciences, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.affiliation: Institute for Biomedical Sciences, Center for Inflammation, Immunity & Infection, Georgia State University, Atlanta, GA 30303, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gewirtz
authors.affiliation: Department of Nutritional Sciences, Pennsylvania State University, University Park, PA 16802, USA; Department of Medicine, Pennsylvania State University Medical Center, Hershey, PA 17033, USA. Electronic address: mvk13@psu.edu.
authors.forename: Matam
authors.initials: M
authors.lastname: Vijay-Kumar
mesh_terms: D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D059305:Diet, High-Fat; D005232:Fatty Acids, Volatile / Q000097:blood; D005243:Feces / Q000737:chemistry; D005260:Female; D007333:Insulin Resistance; D007422:Intestines / Q000382:microbiology; D050155:Lipogenesis; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D064307:Microbiota; D019301:Oleic Acid / Q000378:metabolism; D013230:Stearoyl-CoA Desaturase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051198:Toll-Like Receptor 5 / Q000172:deficiency / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D005232:Fatty Acids, Volatile; D051198:Toll-Like Receptor 5; D019301:Oleic Acid; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase
keywords: Toll-like receptor 5; gut bacteria; hepatic neutral lipids; low-grade inflammation; metabolic diseases; monounsaturated fatty acids; short-chain fatty acids