Nanoplastics disrupt hepatic lipid metabolism via the inhibition of PPARγ: a study based on digestive system exposure

Nanoplastics (NPs) are emerging environmental contaminants capable of crossing biological barriers and accumulating in organs such as the liver, raising growing concerns about their potential contribution to nonalcoholic fatty liver disease (NAFLD). Notably, bottled water has been recognised as a major daily source of NP exposure. However, the associations between NP exposure and NAFLD onset, as well as the mechanistic basis, remain unclear. To investigate this, we analysed data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 cycles, using daily bottled water intake to estimate NP exposure and the hepatic steatosis index (HSI) as an indicator of liver fat accumulation. Animal and cellular experiments were conducted to evaluate NP-induced hepatic alterations. Additionally, transcriptomic analysis of liver tissues was performed, and integration with DisGeNET and the Comparative Toxicogenomics Database (CTD) enabled bioinformatic analyses and identification of key regulatory pathways. Epidemiological results revealed a significant positive correlation between bottled water consumption and HSI. Experimental findings demonstrated that NP exposure induced liver vacuolisation, oxidative damage, metabolic disruption, and inflammation in both in vivo and in vitro models. Transcriptomic and database integration revealed that NP exposure suppressed the PPAR signalling pathway, particularly by downregulating PPARγ expression, with excessive ROS generation likely contributing to this inhibition. These results were summarised in an adverse outcome pathway (AOP) framework, illustrating how NP exposure may impair PPARγ signalling and promote hepatic lipid accumulation. In conclusion, this study provides evidence that environmental NP exposure may be a contributing factor to NAFLD development and highlights the potential public health impact of the intake of NPs from bottled water.