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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 983-996 |
| Number of pages | 14 |
| Journal | Cell Metabolism |
| Volume | 22 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2015 |
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Keywords
- Toll-like receptor 5
- gut bacteria
- hepatic neutral lipids
- low-grade inflammation
- metabolic diseases
- monounsaturated fatty acids
- short-chain fatty acids
ASJC Scopus subject areas
- Physiology
- Molecular Biology
- Cell Biology
Cite this
Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice. / Singh, Vishal; Chassaing, Benoit; Zhang, Limin; San Yeoh, Beng; Xiao, Xia; Kumar, Manish; Baker, Mark T.; Cai, Jingwei; Walker, Rachel; Borkowski, Kamil; Harvatine, Kevin J.; Singh, Nagendra; Shearer, Gregory C.; Ntambi, James M.; Joe, Bina; Patterson, Andrew D.; Gewirtz, Andrew T.; Vijay-Kumar, Matam.
In: Cell Metabolism, Vol. 22, No. 6, 01.01.2015, p. 983-996.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice
AU - Singh, Vishal
AU - Chassaing, Benoit
AU - Zhang, Limin
AU - San Yeoh, Beng
AU - Xiao, Xia
AU - Kumar, Manish
AU - Baker, Mark T.
AU - Cai, Jingwei
AU - Walker, Rachel
AU - Borkowski, Kamil
AU - Harvatine, Kevin J.
AU - Singh, Nagendra
AU - Shearer, Gregory C.
AU - Ntambi, James M.
AU - Joe, Bina
AU - Patterson, Andrew D.
AU - Gewirtz, Andrew T.
AU - Vijay-Kumar, Matam
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Toll-like receptor 5
KW - gut bacteria
KW - hepatic neutral lipids
KW - low-grade inflammation
KW - metabolic diseases
KW - monounsaturated fatty acids
KW - short-chain fatty acids
UR - http://www.scopus.com/inward/record.url?scp=84951733419&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951733419&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2015.09.028
DO - 10.1016/j.cmet.2015.09.028
M3 - Article
VL - 22
SP - 983
EP - 996
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -