DIBAROR

Bile acids targeting Retinoic Related Orphan Receptor gamma for the Treatment of Obesity associated Insulin Resistance and Type 2 Diabetes

Coordinatore	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	159˙065 €
EC contributo	145˙697 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-PoC
Funding Scheme	CSA-SA(POC)
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-04-01   -   2013-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZURICH  Organization address address: Raemistrasse 101 city: ZUERICH postcode: 8092 contact info Titolo: Prof. Nome: Christian Cognome: Wolfrum Email: send email Telefono: +41 44 655 74 51	CH (ZUERICH)	hostInstitution	145˙697.00

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 Obiettivo del progetto (Objective)

'Within the past three years as part of the ERC funding, we have performed extensive research to identify novel factors that might influence adipogenesis and thus control development of obesity and associated metabolic disorders. One of the factors we identified in a translational approach, was the transcription factor retinoic acid orphan receptor gamma (RORγ) which regulates fat cell formation in mice and humans. RORγ is considered as an orphan nuclear receptor as only weak natural ligands that antagonize receptor function have been identified so far. We were able to identify a high affinity natural occurring ligand (Ba1) which is a bile acid isoform and which potently represses the activity of RORγ. Genetic ablation of RORγ expression can rescue obesity associated development of type 2 diabetes, similarly in mice Ba1 supplementation of the diet, prevents the development of diet induced type 2 diabetes. Thus, Ba1 is a ligand for RORγ that has the potential to serve as a therapeutic agent for the treatment of obesity associated insulin resistance and type 2 diabetes. With this application we would add value to the current state of the project in different aspects. We plan to perform a toxicological assessment of Ba1 which will show if it can enter further development without problems. In parallel a set of well-defined Ba1 analogs will be synthesized with the aim to widen our IP position. Furthermore, we plan a detailed evaluation of the in vitro and in vivo efficacy of the newly synthesized Ba1 analogues. We anticipate that it will be possible to implement this naturally occurring bile acid in the context of two separate therapies. Ba1 can be envisioned to be employed as a nutraceutical in common foods. Also, Ba1 could find a niche in the ever-expanding over-the-counter market. Ba1 or modified derivatives may also be useful as stand-alone medication, to treat metabolic co-morbidities such as type 2 diabetes associated with obesity.'