P16 AND METABOLISM

The role of p16INK4a in the development of obesity and insulin resistance

Coordinatore	INSTITUT PASTEUR DE LILLE FONDATION    more  Organization address address: 1 Rue du professeur Calmette city: LILLE postcode: 59019 contact info Titolo: Dr. Nome: Fabienne Cognome: Jean Email: send email Telefono: +33-3-20 87 72 27 Fax: +33-3-20 87 78 73
Nazionalità Coordinatore	France [FR]
Totale costo	164˙310 €
EC contributo	164˙310 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-IEF-2008
Funding Scheme	MC-IEF
Anno di inizio	2009
Periodo (anno-mese-giorno)	2009-03-02   -   2011-03-01

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT PASTEUR DE LILLE FONDATION  Organization address address: 1 Rue du professeur Calmette city: LILLE postcode: 59019 contact info Titolo: Dr. Nome: Fabienne Cognome: Jean Email: send email Telefono: +33-3-20 87 72 27 Fax: +33-3-20 87 78 73	FR (LILLE)	coordinator	164˙310.52

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Genome-wide association studies have linked the CDKN2A locus to an increased risk of Type 2 Diabetes (T2D), which is mostly accompanied by insulin resistance (IR) and obesity. The CDKN2A locus encodes p16INK4a, a tumor suppressor. p16INK4a is an inhibitor of cyclin-dependent kinases, which regulate the cell cycle. Recent studies have shown a link between p16INK4a and the control of inflammation. T2D is an inflammatory disease, in which macrophages are important effector cells. Moreover, adipose tissue macrophages (ATMs) have been found necessary and sufficient for IR to develop. Resident ATMs are known to display an anti-inflammatory “M2” phenotype. Upon obesity, a switch towards a pro-inflammatory “M1” phenotype has been described, inducing adipocyte dysfunction and systemic IR. Additionally, recent findings from the host laboratory indicate that macrophages lacking p16INK4a exhibit a M2 phenotype. Therefore, we hypothesize that p16INK4a may play a role in the development of IR and obesity, possibly by influencing macrophage polarization. To study the role of macrophage p16INK4a in obesity and IR, we will perform a series of bone marrow transplantation experiments, creating mice that lack p16INK4a immune cells (like ATMs) but not in other cells of the body. Several metabolic parameters, like insulin and glucose tolerance, will be analyzed in vivo. Tissues of these animals will be examined thoroughly on mRNA and protein level. The molecular mechanisms of p16INK4a action on macrophage polarization will be further investigated with microarray analysis of isolated ATMs. In addition, the effects of p16INK4a deficient macrophages on adipocytes will be determined in vitro via direct and indirect co-culture experiments. Finally, using this experimental setup of co-culture, the influence of peroxisome proliferator activated receptors on the interplay between ATMs and adipocytes will be determined.'