The nexus of environmental endocrine-disrupting chemical exposure and metabolic dysfunction-associated steatotic liver disease: An emerging public health challenge

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has reached epidemic proportions, creating a substantial healthcare burden. While traditionally attributed to caloric excess and sedentary lifestyles, the incomplete explanation provided by these factors alone has spurred the investigation of novel etiological agents. There is now compelling evidence that chronic, low-dose exposure to environmental endocrine-disrupting chemicals (EDCs) is a significant and underappreciated risk factor driving MASLD pathogenesis. This review synthesizes the current human epidemiological and mechanistic evidence, focusing on the last five years, to elucidate the role of both established EDCs (e.g., phthalates, bisphenols, PFAS, organochlorine pesticides) and emerging contaminants, notably micro- and nanoplastics (MNPs). We detail how these pervasive pollutants promote hepatic steatosis, inflammation, and fibrosis by disrupting nuclear receptor signaling (e.g., PPARγ), inducing gut dysbiosis and barrier dysfunction, causing mitochondrial and lysosomal impairment, and reprogramming lipid metabolism. The review highlights that MNPs, in particular, represent a frontier in environmental hepatotoxicity, with recent data revealing their ability to bioaccumulate and exacerbate metabolic insults through novel mechanisms. By integrating evidence from population studies and experimental models, this review underscores the necessity of incorporating the "exposome" into the MASLD etiological framework. It concludes that mitigating this public health challenge requires concerted efforts in advancing research on chemical mixtures and critical exposure windows, alongside implementing policies aimed at reducing environmental exposure.