Nuclear Receptor Signaling in the Treatment of Liver and Metabolic Disorders
Event details
| Date | 20.03.2017 |
| Hour | 13:30 › 14:30 |
| Speaker | Bart STAELS Univ. Lille - European Genomic Institute for Diabetes (E.G.I.D) ; INSERM UMR 1011 ; CHU Lille; Institut Pasteur de Lille, F-59000 Lille, France |
| Location | |
| Category | Conferences - Seminars |
SEMINAR SERIES : Trends in Physiology and Metabolism (Bio-682)
Abstract:
Bile acids (BA) exert important functions in the entero-hepatic system. BA are synthesized and conjugated in the liver, secreted in the duodenum after meal ingestion, modified by the intestinal 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.
BA pool size and composition are modulated by metabolic perturbations, being altered in obesity, insulin-resistance, type 2 diabetes and non-alcoholic steatohepatitis (NASH) in preclinical models and humans. BA sequestrants, which interrupt the entero-hepatic BA circulation, improve lipid/glucose homeostasis. Modification 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.
BA modulate metabolism in part through activation of the nuclear receptor Farnesoid X Receptor (FXR) and the membrane receptor TGR5. BA and FXR regulate metabolism via entero-hepatic signalling. FXR protects the liver from BA overflow by regulating BA synthesis, secretion and transport. In the intestine, BA bind to FXR in ileal enterocytes to induce FGF15/19 expression which in turn inhibits hepatic BA synthesis. In the liver, FXR also regulates glucose and lipid metabolism. Moreover, FXR signalling contributes to the changes in gut microbial communities and the metabolic benefits of vertical sleeve gastrectomy. Furthermore, microbiota-modified BA not only act in the gut, but also on the entero-hepatic system to control hepatic BA metabolism and obesity. Intestinal FXR signalling also modulates NASH. We recently reported FXR expression in the entero-endocrine tissue, specifically in entero-endocrine L cells, where FXR inhibits the response to glucose on the production and secretion of the incretin GLP-1. These studies established the importance of BA signalling through FXR in the intestine and the potential of FXR antagonism in the treatment of metabolic diseases.
Abstract:
Bile acids (BA) exert important functions in the entero-hepatic system. BA are synthesized and conjugated in the liver, secreted in the duodenum after meal ingestion, modified by the intestinal 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.
BA pool size and composition are modulated by metabolic perturbations, being altered in obesity, insulin-resistance, type 2 diabetes and non-alcoholic steatohepatitis (NASH) in preclinical models and humans. BA sequestrants, which interrupt the entero-hepatic BA circulation, improve lipid/glucose homeostasis. Modification 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.
BA modulate metabolism in part through activation of the nuclear receptor Farnesoid X Receptor (FXR) and the membrane receptor TGR5. BA and FXR regulate metabolism via entero-hepatic signalling. FXR protects the liver from BA overflow by regulating BA synthesis, secretion and transport. In the intestine, BA bind to FXR in ileal enterocytes to induce FGF15/19 expression which in turn inhibits hepatic BA synthesis. In the liver, FXR also regulates glucose and lipid metabolism. Moreover, FXR signalling contributes to the changes in gut microbial communities and the metabolic benefits of vertical sleeve gastrectomy. Furthermore, microbiota-modified BA not only act in the gut, but also on the entero-hepatic system to control hepatic BA metabolism and obesity. Intestinal FXR signalling also modulates NASH. We recently reported FXR expression in the entero-endocrine tissue, specifically in entero-endocrine L cells, where FXR inhibits the response to glucose on the production and secretion of the incretin GLP-1. These studies established the importance of BA signalling through FXR in the intestine and the potential of FXR antagonism in the treatment of metabolic diseases.
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Practical information
- Informed public
- Free
Organizer
- Prof. Lluis Fajas (UNIL), Prof. Kei Sakamoto (NIHS) and Prof. Kristina Schoonjans (EPFL)
Contact
- Prof. Kristina Schoonjans (EPFL) - [email protected]