Bisphenols perturb systemic iron homeostasis and fuel the pathogenesis of metabolic dysfunction-associated steatotic liver disease

Abstract

The pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) arises from the interplay between environmental and nutritional factors. This review, from a novel “pollutant-nutrient-disease” perspective, systematically elucidates the core mechanisms by which bisphenols (BPs) exposure exacerbates MASLD through the disruption of iron homeostasis. Evidence indicates that BPs not only directly induce hepatic injury but also, through the activation of pathways such as GPER, lead to dysregulation of hepatic hepcidin and abnormal intestinal iron absorption, resulting in a unique state of “hepatic iron overload-systemic iron deficiency.” This iron metabolic disorder synergizes with BPs toxicity, collectively amplifying oxidative stress, inflammation, and gut-liver axis dysfunction, thereby accelerating MASLD progression. Future studies should employ multi-omics approaches and population-based cohorts to dissect the interaction networks and explore novel interventions targeting iron metabolism.