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EpiFAT SIGNED

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

Total Cost €

EC-Contrib. €

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.

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

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 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.	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

List of publications.
year	authors and title	journal	last update
2019	BÃ©nÃ©dicte 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, FrÃ©dÃ©ric Matonti, Marie Houssays, Louisa Goumidi, Lucile Vignaud, Xavier Guillonneau, Ali Erginay, BÃ©nÃ©dicte Dupas, Marie-Louise Jennifer, Marianne AutiÃ©, 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-FranÃ§ois 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 GoÃ±i, Zhiqiang Huang, Lise-Lotte Vedin, Tomas Jakobsson, Marco Giudici, Osman Ahmed, Matteo Pedrelli, Serena Barilla, Fawaz Alzaid, Arturo Mendoza, Tarja SchrÃ¶der, 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 PPARÎ± published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-019-09524-z	Nature Communications 10/1	2019-06-06
2018	JÃ©rÃ´me Gilleron, GwennaÃ«lle Bouget, Stoyan Ivanov, Cindy Meziat, Franck Ceppo, Bastien Vergoni, Mansour Djedaini, Antoine Soprani, Karine Dumas, Arnaud Jacquel, Laurent Yvan-Charvet, Nicolas Venteclef, Jean-FranÃ§ois 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, RaphaÃ«lle 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-FranÃ§ois 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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