ImmunoBile SIGNED
Bile acid, immune-metabolism, lipid and glucose homeostasis
Total Cost €
0EC-Contrib. €
0Partnership
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Project "ImmunoBile" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITE DE LILLE II - DROIT ET SANTE
There are not information about this coordinator. Please contact Fabio for more information, thanks. |
| Coordinator Country | France [FR] |
| Total cost | 2˙500˙000 € |
| EC max contribution | 2˙500˙000 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2015-AdG |
| Funding Scheme | ERC-ADG |
| Starting year | 2016 |
| Duration (year-month-day) | from 2016-09-01 to 2021-08-31 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITE DE LILLE | FR (LILLE) | coordinator | 2˙500˙000.00 |
| 2 | UNIVERSITE DE LILLE II - DROIT ET SANTE | FR (Lille) | coordinator | 0.00 |
Map
Project objective
The role of chronic inflammation in obesity, metabolic and cardiovascular diseases is increasingly recognized. Bile acids (BA), synthesized in the liver and modified by the gut flora, facilitate lipid absorption in the intestine. BA modulate lipid and glucose homeostasis by activating the nuclear receptor FXR and the GPCR TGR5. Intriguingly, peripheral BA concentrations are elevated in type 2 diabetes (T2D) and FXR mediates the beneficial metabolic response to gastric bypass in mice. The immune system plays an important role in the cross-talk with metabolic tissues, such as liver, intestine and adipose tissues. However, whether BA modulate immune cell function is unknown. Our unpublished results identifying FXR and TGR5 expression in lymphoid cells, prompt us to study their role in the regulation of glucose and lipid metabolism through immune cell modulation. Using reporter mice and specific ligands, we will characterize the immune cells expressing active FXR and TGR5. We will determine their role in metabolism and inflammation by immune cell-specific gene inactivation in models of obesity, T2D and elevated peripheral blood BA concentrations. Mass cytometry, cell sorting and single cell transcriptomic analysis will allow the identification of gene networks regulated by BA and their receptors. As microbiota generate biologically active secondary BA, we will assess the impact of microbiota depletion and subsequent BA acid pool modifications on immune cell populations. Translational studies in humans with altered BA metabolism and pharmacological treatment with anti-diabetic BA sequestrants will allow assessment of alterations in immune functions. This project aims to identify an hitherto unexplored role of BA through modulation of the immune system on T2D, NAFLD and dyslipidemia. Success of the project critically depends on an integrative approach uniquely undertaken in my laboratory through its unique multidisciplinary expertise in basic and translational biology.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2017 |
Oscar Chávez-Talavera, Anne Tailleux, Philippe Lefebvre, Bart Staels Bile Acid Control of Metabolism and Inflammation in Obesity, Type 2 Diabetes, Dyslipidemia, and Nonalcoholic Fatty Liver Disease published pages: 1679-1694.e3, ISSN: 0016-5085, DOI: 10.1053/j.gastro.2017.01.055 |
Gastroenterology 152/7 | 2019-08-06 |
| 2017 |
Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loïc Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux, Julie Charton Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose Tolerance published pages: 4185-4211, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.6b01873 |
Journal of Medicinal Chemistry 60/10 | 2019-08-06 |
| 2018 |
Maheul Ploton, Claire Mazuy, Céline Gheeraert, Vanessa Dubois, Alexandre Berthier, Julie Dubois-Chevalier, Xavier Maréchal, Kadiombo Bantubungi, Hélène Diemer, Sarah Cianférani, Jean-Marc Strub, Audrey Helleboid-Chapman, Jérôme Eeckhoute, Bart Staels, Philippe Lefebvre The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis published pages: 1099-1109, ISSN: 0168-8278, DOI: 10.1016/j.jhep.2018.06.022 |
Journal of Hepatology 69/5 | 2019-08-06 |
| 2018 |
Benoit Pourcet, Mathilde Zecchin, Lise Ferri, Justine Beauchamp, Sadicha Sitaula, Cyrielle Billon, Stéphane Delhaye, Jonathan Vanhoutte, Alicia Mayeuf-Louchart, Quentin Thorel, Joel T. Haas, Jérome Eeckhoute, David Dombrowicz, Christian Duhem, Alexis Boulinguiez, Steve Lancel, Yasmine Sebti, Thomas P. Burris, Bart Staels, Hélène M. Duez Nuclear Receptor Subfamily 1 Group D Member 1 Regulates Circadian Activity of NLRP3 Inflammasome to Reduce the Severity of Fulminant Hepatitis in Mice published pages: 1449-1464.e20, ISSN: 0016-5085, DOI: 10.1053/j.gastro.2017.12.019 |
Gastroenterology 154/5 | 2019-06-13 |
| 2018 |
Emilie Catry, Laure B Bindels, Anne Tailleux, Sophie Lestavel, Audrey M Neyrinck, Jean-François Goossens, Irina Lobysheva, Hubert Plovier, Ahmed Essaghir, Jean-Baptiste Demoulin, Caroline Bouzin, Barbara D Pachikian, Patrice D Cani, Bart Staels, Chantal Dessy, Nathalie M Delzenne Targeting the gut microbiota with inulin-type fructans: preclinical demonstration of a novel approach in the management of endothelial dysfunction published pages: 271-283, ISSN: 0017-5749, DOI: 10.1136/gutjnl-2016-313316 |
Gut 67/2 | 2019-06-13 |
| 2017 |
Julie Dubois-Chevalier, Vanessa Dubois, Hélène Dehondt, Parisa Mazrooei, Claire Mazuy, Aurélien A. Sérandour, Céline Gheeraert, Penderia Guillaume, Eric Baugé, Bruno Derudas, Nathalie Hennuyer, Réjane Paumelle, Guillemette Marot, Jason S. Carroll, Mathieu Lupien, Bart Staels, Philippe Lefebvre, Jérôme Eeckhoute The logic of transcriptional regulator recruitment architecture at cis -regulatory modules controlling liver functions published pages: 985-996, ISSN: 1088-9051, DOI: 10.1101/gr.217075.116 |
Genome Research 27/6 | 2019-06-13 |
| 2017 |
Alicia Mayeuf-Louchart, Quentin Thorel, Stéphane Delhaye, Justine Beauchamp, Christian Duhem, Anne Danckaert, Steve Lancel, Benoit Pourcet, Estelle Woldt, Alexis Boulinguiez, Lise Ferri, Mathilde Zecchin, Bart Staels, Yasmine Sebti, Hélène Duez Rev-erb-α regulates atrophy-related genes to control skeletal muscle mass published pages: , ISSN: 2045-2322, DOI: 10.1038/s41598-017-14596-2 |
Scientific Reports 7/1 | 2019-06-13 |
| 2018 |
Benoit Pourcet, Bart Staels Alternative macrophages in atherosclerosis: not always protective! published pages: 910-912, ISSN: 0021-9738, DOI: 10.1172/JCI120123 |
Journal of Clinical Investigation 128/3 | 2019-06-13 |
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