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EpiFAT SIGNED

Epigenomic Reprogramming of Adipose Tissue Function and Energy Metabolism in Type 2 Diabetes

Total Cost €

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EC-Contrib. €

0

Partnership

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 EpiFAT project word cloud

Explore the words cloud of the EpiFAT project. It provides you a very rough idea of what is the project "EpiFAT" about.

epigenetics    onset    mouse    genome    histone    environmental    hyperplasia    disease    anticipate    organ    treatment    epigenomic    transcriptional    protein    altered    discovery    tissue    dysfunction    issue    modifiers    candidates    coregulators    adipokines    gene    disturbances    functions    combination    6b    expression    hypertrophy    pathologies    obesity    human    susceptibility    search    kdm6b    humans    dysregulation    obese    differ    influencing    progression    environment    individual    clinically    documented    demethylase    underpinning    inflammatory    secretion    sufficiently    suppressor    gps2    leads    function    prevention    lysine    diabetes    mechanisms    modifications    models    jmjd3    closely    strategies    subsequently    hypothesis    linked    inflammation    dissect    underlying    poorly    macrophages    t2d    molecular    mainly    metabolic    pathogenesis    explanation    link    thereby    mechanism    adipocytes    reprogramming    epigenetic    adipose    influence   

Project "EpiFAT" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-06-01   to  2022-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 2˙000˙000.00

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 Project objective

Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes (T2D). The mechanisms underlying the development of obesity and T2D include the hypertrophy and/or hyperplasia of adipocytes and adipose tissue inflammation together with an altered secretion of adipokines. However, the explanation of why individual obese (and some non-obese) humans differ in their susceptibility to develop T2D is still an issue that is currently not sufficiently addressed. This susceptibility to T2D is mainly associated with environmental factors. One link between environment and disease is epigenetics influencing gene expression and subsequently organ dysfunction. Epigenetic modifications in adipose tissue have been proposed to influence the susceptibility to T2D. However, the epigenomic mechanisms underpinning adipose tissue dysfunction are poorly known. In search for epigenomic modifiers that control adipose tissue function and also impact on T2D pathogenesis, we have recently identified the transcriptional coregulators GPS2 (G-Protein Pathway Suppressor 2) and KDM6B (Histone Lysine Demethylase 6B, also called JMJD3) as strong candidates. Our hypothesis is that the clinically documented dysregulation of GPS2 (down) and KDM6B (up) expression and function during obesity leads to the closely linked epigenetic and transcriptional reprogramming of adipocytes and adipose tissue-macrophages, thereby enhancing the susceptibility to metabolic and inflammatory disturbances and the progression towards T2D. We propose here to test this hypothesis using the combination of unique mouse models, genome-wide molecular and epigenomic analyses and human studies to dissect the epigenomic functions of GPS2 and KDM6B in adipose tissue, aiming at identifying mechanism involved in the development T2D. Thereby, we anticipate the discovery of novel epigenomic targets for future prevention and treatment strategies in metabolic dysfunction.

 Publications

year authors and title journal last update
List of publications.
2019 Bénédicte Gaborit, Jean-Baptiste Julla, Samaher Besbes, Matthieu Proust, Clara Vincentelli, Benjamin Alos, Patricia Ancel, Fawaz Alzaid, Rodrigue Garcia, Philippe Mailly, Florence Sabatier, Maud Righini, Pierre Gascon, Frédéric Matonti, Marie Houssays, Louisa Goumidi, Lucile Vignaud, Xavier Guillonneau, Ali Erginay, Bénédicte Dupas, Marie-Louise Jennifer, Marianne Autié, Tiphaine Vidal-Trec
Glucagon-like peptide 1 receptor agonists, diabetic retinopathy and angiogenesis: The AngioSafe type 2 diabetes study
published pages: , ISSN: 0021-972X, DOI: 10.1210/clinem/dgz069
The Journal of Clinical Endocrinology & Metabolism 2020-01-30
2019 Karima Drareni, Jean-François Gautier, Nicolas Venteclef, Fawaz Alzaid
Transcriptional control of macrophage polarisation in type 2 diabetes
published pages: , ISSN: 1863-2297, DOI: 10.1007/s00281-019-00748-1
Seminars in Immunopathology 2019-06-06
2019 Ning Liang, Anastasius Damdimopoulos, Saioa Goñi, Zhiqiang Huang, Lise-Lotte Vedin, Tomas Jakobsson, Marco Giudici, Osman Ahmed, Matteo Pedrelli, Serena Barilla, Fawaz Alzaid, Arturo Mendoza, Tarja Schröder, Raoul Kuiper, Paolo Parini, Anthony Hollenberg, Philippe Lefebvre, Sven Francque, Luc Van Gaal, Bart Staels, Nicolas Venteclef, Eckardt Treuter, Rongrong Fan
Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09524-z
Nature Communications 10/1 2019-06-06
2018 Jérôme Gilleron, Gwennaëlle Bouget, Stoyan Ivanov, Cindy Meziat, Franck Ceppo, Bastien Vergoni, Mansour Djedaini, Antoine Soprani, Karine Dumas, Arnaud Jacquel, Laurent Yvan-Charvet, Nicolas Venteclef, Jean-François Tanti, Mireille Cormont
Rab4b Deficiency in T Cells Promotes Adipose Treg/Th17 Imbalance, Adipose Tissue Dysfunction, and Insulin Resistance
published pages: 3329-3341.e5, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.11.083
Cell Reports 25/12 2019-03-18
2018 Karima Drareni, Raphaëlle Ballaire, Serena Barilla, Mano J. Mathew, Amine Toubal, Rongrong Fan, Ning Liang, Catherine Chollet, Zhiqiang Huang, Maria Kondili, Fabienne Foufelle, Antoine Soprani, Ronan Roussel, Jean-François Gautier, Fawaz Alzaid, Eckardt Treuter, Nicolas Venteclef
GPS2 Deficiency Triggers Maladaptive White Adipose Tissue Expansion in Obesity via HIF1A Activation
published pages: 2957-2971.e6, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2018.08.032
Cell Reports 24/11 2019-03-11

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