The project: Role of Chemical Endocrine Disruptors (EDCs) on Metabolically Associated Fatty Liver Disease (MASLD).
MASLD is the condition of excessive hepatic fat accumulation unrelated to alcohol intake, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH). With a prevalence of 25% in the general population, MASLD is currently the most common liver disease and poses a significant health and economic burden. While hyperlipidaemia, obesity and insulin resistance are the main risk factors for this disease and contribute to its increasing prevalence, there is growing evidence that exposure to endocrine-disrupting chemicals (EDCs) may initiate and/or lead to the progression of MASLD. The EDC-MASLD project will investigate the impact of environmental exposure to EDCs on the internal exposome and the degree of liver damage in MASLD in prospective study settings, focusing on the transition period to the progressive stages of MASLD. EDC-MASLD focuses mainly on the interactions between EDC exposure, sex, genotype, diet, and socio-economic and lifestyle factors. EDC exposure studies will be performed in murine models of MASLD to understand their respective mechanisms of action and develop new EDC screening tools. This project is funded by the European Union and is part of a collaborative consortium including internationally known groups in the field of MASLD and EDCs toxicity.

Job description (duties and tasks):

The Obesity and Metabolic Regulation Laboratory led by Prof. Antonio Vidal-Puig (https://www.cipf.es/science/investigacion/unidades-mixtas/unidad-mixta-cipf-cambridge-obesidad-y-regulacion-metabolica?lang=es) and the Obesity, Diabetes and Comorbidities Laboratory led by Dr Stefania Carobbio (https://www.cipf.es/science/investigacion/trastornos-metabolicos/obesidad-diabetes-y-comorbilidades?lang=es) offer a postdoctoral researcher position in a project (EDC-MASLD) investigating the chronic effects of EDCs on the progression of MASLD in vivo. MASLD is induced with a specific diet composition. Therefore, experiments will be conducted using a control diet (Altromin 1324) and the Gubra amylin NASH diet (GAN). Control and GAN diet-fed mice will receive EDC chronically. In vivo phenotypic characterisation: To characterise the impact of EDC on disease progression, mice will undergo body weight monitoring, blood biochemistry, glucose/insulin tolerance testing, assessment of energy expenditure (by indirect calorimetry) and histological examination of liver tissue after sacrifice. Ex vivo phenotyping: histopathological analysis of the, using standard histology and immunohistochemistry (IHC) analysis to assess the state of inflammation and fibrosis of the liver, as well as qPCR and western blotting for immunological, inflammatory and stress markers. The postdoctoral researcher will also benefit of scientific interactions and collaboration with the laboratory of Prof Vidal-Puig at the Institute of Metabolic Science in Cambridge, UK and will engage in the research initiatives the laboratories at CIPF have there.

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