Investigation of Endocrine-Disrupting Chemicals as Contributors to Progression of Metabolic Dysfunction Associated Steatotic Liver Disease (EDC-MASLD)

MASLD是与酒精摄入无关的肝脏脂肪过度积累的病症，范围从简单的脂肪变性到代谢功能障碍相关的脂肪性肝炎（MASH）。MASLD在一般人群中的患病率为25%，是目前最常见的肝病，也是主要的医疗保健和经济负担。虽然糖尿病、肥胖和胰岛素抵抗是MASLD的主要风险因素，并导致其患病率上升，但越来越多的证据表明，暴露于内分泌干扰物（EDCs）可引发和/或导致MASLD的进展。EDC-MASLD将专注于研究环境暴露于EDCs对内部代谢组（代谢组，肠道微生物组，表观基因组，蛋白质组，免疫组）的影响以及前瞻性研究环境中MASLD的肝损伤程度，重点关注MASLD向进展阶段的过渡期。EDC-MASLD特别关注EDC暴露、性别、基因型、饮食、社会经济和生活方式因素之间的相互作用，通过独特的欧洲NAFLD登记处提供的数据和生物样本，该登记处包括9，000多名具有组织学特征的MASLD患者。将在MASLD小鼠模型、斑马鱼模型和人2D/3D体外模型中进行EDC暴露研究，旨在了解各自的作用机制并开发新型EDC筛选工具。EDC-MASLD联盟在肝病学、内分泌学、毒理学、代谢组学研究、代谢组学、系统生物学、环境经济学和通信与技术研究领域拥有多样化和互补的专业知识，各自的PI都是各自领域的全球领导者。总之，EDC-MASLD将大大有助于以确定和机械评估EDCs影响为中心的行动，监测和减少接触的战略，以及可以更好地保护人类和环境健康的监管行动。

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.