Cel 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. Dziedzina nauki medical and health sciencesclinical medicineendocrinologydiabetesmedical and health sciencesbasic medicinepathologymedical and health scienceshealth sciencesnutritionobesitynatural sciencesbiological sciencesgeneticsepigenetics Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-2016-COG - ERC Consolidator Grant Zaproszenie do składania wniosków ERC-2016-COG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-COG - Consolidator Grant Koordynator INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Wkład UE netto € 2 000 000,00 Adres Rue de tolbiac 101 75654 Paris Francja Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 2 000 000,00 Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE Francja Wkład UE netto € 2 000 000,00 Adres Rue de tolbiac 101 75654 Paris Zobacz na mapie Region Ile-de-France Ile-de-France Paris Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 2 000 000,00