Overview of the hazardous impacts of metabolism-disrupting chemicals on the progression of fatty liver diseases.

BACKGROUND: Given the global increase in obesity, metabolic dysfunction-associated steatotic liver disease (MASLD) is a major health concern. Because the liver is the primary organ for xenobiotic metabolism, the impact of environmental stressors on liver homeostasis and MASLD has garnered significant interest over the past few decades. The concept of metabolism-disrupting chemicals (MDCs) has been introduced to underscore the importance of environmental factors in metabolic homeostasis. Recent epidemiological and biological studies suggest a causal link between exposure to MDCs and prevalence and progression of MASLD. OBJECTIVE: This review aims to introduce the emerging concept of MDCs and their representative toxic mechanisms. In particular, this review focuses on broadening the understanding of their impacts on MASLD or metabolic dysfunction-associated steatohepatitis (MASH) progression. RESULT: Recent research has highlighted the environmental contaminants, such as heavy metals, microplastics, and pesticides, have the potential to influence hepatic metabolism and aggravate MASLD/MASH progression. These MDCs not only directly affect lipid metabolism in hepatocytes but also affect other cell types, such as immune cells and stellate cells, as well as the gut-liver axis. CONCLUSION: Collectively, these findings contribute to establishing a well-defined adverse outcome pathway and identify novel therapeutic options for liver diseases associated with pollutants.