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Investigation of endocrine-disrupting chemicals as contributors to progression of metabolic dysfunction-associated steatotic liver disease

Project description

Identifying the impact of endocrine-disrupting chemicals on MASLD

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterised by excessive fat accumulation in the liver unrelated to alcohol, affecting 25 % of the population, with obesity and insulin resistance as major risk factors. The EU-funded EDC-MASLD project will investigate the impact of endocrine-disrupting chemicals (EDCs) on the internal exposome (metabolome, gut microbiome, epigenome, proteome, and immunome) and their contribution to liver damage in MASLD. Focusing on the progression of MASLD, the project will analyse the interplay between EDC exposure and factors such as sex, genotype, diet, and socio-economic status. It will use data from the European NAFLD Registry, which includes over 9 000 patients, as well as murine models, zebrafish, and human in vitro studies to explore underlying mechanisms and develop new EDC screening tools.

Objective

MASLD is the condition of excessive accumulation of liver fat unrelated to alcohol intake, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH). With a 25% prevalence in the general population, MASLD is currently the most common liver disease, and a major healthcare and economic burden. While hyperlipidaemia, obesity and insulin resistance are the major risk factors for MASLD and contribute to its rising prevalence, growing evidence suggests that exposure to endocrine-disrupting chemicals (EDCs) can initiate and/or cause progression of MASLD. EDC-MASLD will focus on investigating the impact of environmental exposure to EDCs on the internal exposome (metabolome, gut microbiome, epigenome, proteome, immunome) and degree of liver damage in MASLD in prospective study settings, with a focus on the period of transition to progressive stages of MASLD. EDC-MASLD is particularly focused on interactions between EDC exposure, sex, genotype, diet, socioeconomic and lifestyle factors, via the data and biosamples available in the unique European NAFLD Registry, comprising over 9,000 patients with histologically characterised MASLD. EDC exposure studies will be performed in murine models of MASLD, zebrafish models, and human 2D/3D in vitro models, with an aim to understand respective mechanisms-of-action and to develop novel EDC screening tools. The EDC-MASLD consortium has diverse and complementary expertise in the domains of hepatology, endocrinology, toxicology, exposome research, metabolomics, systems biology, environmental economics, and communications & technology research, with respective PIs being global leaders in their fields. Taken together, EDC-MASLD will significantly contribute to the actions centred on identification and mechanistic assessment of impact of EDCs, strategies to monitor and reduce exposure, and regulatory actions that could better protect human and environmental health.

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Keywords

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Topic(s)

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HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

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(opens in new window) HORIZON-HLTH-2023-ENVHLTH-02

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Coordinator

OREBRO UNIVERSITY
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 578 570,00
Address
FAKULTETSGATAN 1
70182 Orebro
Sweden

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Region
Östra Sverige Östra Mellansverige Örebro län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 578 570,00

Participants (13)

Partners (1)

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