Cel Obesity is associated with increased risk for epithelial tumors such as hepatocellular carcinoma (HCC). It is not known, however, whether obesity increases the risk for HCC simply because it promotes cirrhosis, a general risk factor for HCC, or through other mechanisms that operate independently of cirrhosis. Among these, obesity is associated with a chronic inflammatory state, with the release of cytokines such as IL-6 and TNFalpha, well-known HCC mediators. Obesity is normally linked to diabetes and in consequence, to hyperinsulinemia. This increase in circulating insulin levels is suggested to be a factor that contributes to cancer. Moreover, the increase in free fatty acids (FFA) in blood among obese patients promotes a compensatory response from liver that activates the transcription of genes required for beta-oxidation, leading to a reduction in non-physiological stores of lipids in the liver. This increase in beta-oxidation could result in oxidative stress, inflammation and the production of lipid peroxidation bioproducts, which are known mutagens. The precise mechanisms whereby FFA and cytosolic triglycerides exert their effects, resulting in the diabetic phenotype, remain poorly understood. Emerging evidence nonetheless links microRNA (miRNA) with lipid metabolism, suggesting that these small RNAs mediate this increase in beta-oxidation.Our goal is to study how the components of the obesity state (inflammation, steatosis hyperinsulinemia and microRNA control of gene regulation) affect HCC development. We will use several mouse models in which one or more of these factors are reduced following induction of metabolic disease. We will also determine whether specific miRNAs that are down- or upregulated in the liver of mice on a high fat diet are implicated in HCC development. Dziedzina nauki medical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculeslipidsmedical and health sciencesclinical medicineoncologymedical and health sciencesclinical medicinehepatologymedical and health scienceshealth sciencesnutritionobesity Program(-y) 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) Temat(-y) ERC-SG-LS4 - ERC Starting Grant - Physiology, Pathophysiology and Endocrinology Zaproszenie do składania wniosków ERC-2010-StG_20091118 Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-SG - ERC Starting Grant Instytucja przyjmująca CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Wkład UE € 1 498 043,00 Adres CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Hiszpania Zobacz na mapie Region Comunidad de Madrid Comunidad de Madrid Madrid Rodzaj działalności Research Organisations Kontakt administracyjny Inga Dreville (Ms.) Kierownik naukowy Guadalupe Sabio Buzo (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE Rozwiń wszystko Zwiń wszystko CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CARLOS III (F.S.P.) Hiszpania Wkład UE € 1 498 043,00 Adres CALLE MELCHOR FERNANDEZ ALMAGRO 3 28029 Madrid Zobacz na mapie Region Comunidad de Madrid Comunidad de Madrid Madrid Rodzaj działalności Research Organisations Kontakt administracyjny Inga Dreville (Ms.) Kierownik naukowy Guadalupe Sabio Buzo (Dr.) Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Koszt całkowity Brak danych
