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

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.