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SUMMARY:Nuclear Receptor Signaling in the Treatment of Liver and Metabolic
  Disorders
DTSTART:20170320T133000
DTEND:20170320T143000
DTSTAMP:20260916T153721Z
UID:4dfca6fd71dd5f6f30e591009aa9283bb6fc6ab4c6c3d096edc66a94
CATEGORIES:Conferences - Seminars
DESCRIPTION:Bart STAELS Univ. Lille - European Genomic Institute for Diabe
 tes (E.G.I.D) \; INSERM UMR 1011 \; CHU Lille\; Institut Pasteur de Lill
 e\, F-59000 Lille\, France\nSEMINAR SERIES :  Trends in Physiology and Me
 tabolism (Bio-682)\n\nAbstract:\nBile acids (BA) exert important functions
  in the entero-hepatic system. BA are synthesized and conjugated in the li
 ver\, secreted in the duodenum after meal ingestion\, modified by the inte
 stinal gut flora\, reabsorbed in the intestine and transported back to the
  liver by the portal vein. Although most BA are recaptured by hepatocytes\
 , a fraction escapes and reaches peripheral organs.\nBA pool size and comp
 osition are modulated by metabolic perturbations\, being altered in obesit
 y\, insulin-resistance\, type 2 diabetes and non-alcoholic steatohepatitis
  (NASH) in preclinical models and humans. BA sequestrants\, which interrup
 t the entero-hepatic BA circulation\, improve lipid/glucose homeostasis. M
 odification of the intestinal microbiota also alters the BA pool in mice. 
 Systemic BA concentrations increase after Roux-en-Y-gastric-bypass (RYGB) 
 surgery in humans and animal models.\nBA modulate metabolism in part throu
 gh activation of the nuclear receptor Farnesoid X Receptor (FXR) and the m
 embrane receptor TGR5. BA and FXR regulate metabolism via entero-hepatic s
 ignalling. FXR protects the liver from BA overflow by regulating BA synthe
 sis\, secretion and transport. In the intestine\, BA bind to FXR in ileal 
 enterocytes to induce FGF15/19 expression which in turn inhibits hepatic B
 A synthesis. In the liver\, FXR also regulates glucose and lipid metabolis
 m. Moreover\, FXR signalling contributes to the changes in gut microbial c
 ommunities and the metabolic benefits of vertical sleeve gastrectomy. Furt
 hermore\, microbiota-modified BA not only act in the gut\, but also on the
  entero-hepatic system to control hepatic BA metabolism and obesity. Intes
 tinal FXR signalling also modulates NASH. We recently reported FXR express
 ion in the entero-endocrine tissue\, specifically in entero-endocrine L ce
 lls\, where FXR inhibits the response to glucose on the production and sec
 retion of the incretin GLP-1. These studies established the importance of 
 BA signalling through FXR in the intestine and the potential of FXR antago
 nism in the treatment of metabolic diseases.\n 
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717
STATUS:CONFIRMED
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