[PMID]: | 29198707 |
[Au] Autor: | Wang F; Lu Z; Wang X; Zhang Y |
[Ad] Endereço: | School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. |
[Ti] Título: | Impaired vagus function in rats suppresses bile acid synthesis in the liver by disrupting tight junctions and activating Fxr-Fgf15 signaling in the intestine. |
[So] Source: | Biochem Biophys Res Commun;495(1):1490-1496, 2018 01 01. |
[Is] ISSN: | 1090-2104 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Bile acids (BAs) circulate between the liver and intestine, and regulate the homeostasis of glucose, lipid, and energy. Recent studies demonstrated an essential role of BAs in neurological diseases, suggesting an interaction between BAs and the nervous system. In the present study, we showed that impaired vagus function in rats induced by vagotomy resulted in an increase in bile flow without causing liver injury. The concentrations of unconjugated and glycine-conjugated BAs were increased in both serum and bile of rats after vagotomy, which was due to impaired tight junctions and thus increased passive absorption of BAs in the intestine. Vagotomy markedly suppressed the expression of the rate-limiting BA synthetic enzyme Cyp7a1, which was not due to activation of Fxr-Shp signaling in the liver, but due to activation of Fxr-Fgf15 signaling in the intestine. Furthermore, vagotomy produced a BA profile in the bile favorable for Fxr activation by decreasing tauro-ß-muricholic acid, a natural Fxr antagonist, and increasing glyco-chenodeoxycholic acid, a natural Fxr agonist. In summary, the present study provides the first comprehensive analysis of the critical role of the vagus nerve in regulating BA metabolism and signaling pathway. |
[Mh] Termos MeSH primário: |
Ácidos e Sais Biliares/secreção Fatores de Crescimento de Fibroblastos/metabolismo Íleo/metabolismo Fígado/secreção Receptores Citoplasmáticos e Nucleares/metabolismo Junções Íntimas/metabolismo Doenças do Nervo Vago/fisiopatologia
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[Mh] Termos MeSH secundário: |
Animais Fígado/patologia Masculino Ratos Ratos Wistar Transdução de Sinais Junções Íntimas/patologia Doenças do Nervo Vago/complicações
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Bile Acids and Salts); 0 (FGF19 protein, rat); 0 (Receptors, Cytoplasmic and Nuclear); 0 (farnesoid X-activated receptor); 62031-54-3 (Fibroblast Growth Factors) |
[Em] Mês de entrada: | 1712 |
[Cu] Atualização por classe: | 180105 |
[Lr] Data última revisão:
| 180105 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 171205 |
[St] Status: | MEDLINE |
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