Integrated transcriptomic and metabolomic analyses to decipher the regulatory mechanisms of polystyrene nanoplastic-induced metabolic disorders in hepatocytes

Abstract

Micro- and nanoplastic (MNP) pollution is a pervasive and growing problem, posing potential health risks to humans. MNPs enter the human body mainly through ingestion, inhalation, and dermal contact. They accumulate in the liver via the circulatory system and disrupt hepatic metabolism. However, the potential mechanisms underlying metabolic dysfunction caused by MNPs in the liver remain poorly understood. In the present study, integrated transcriptomic and metabolomic approaches were used to address the regulatory mechanisms of polystyrene nanoplastic (PSNP)-induced metabolic disorders in hepatocytes. First, transcriptomic analysis demonstrated the enriched pathways related to fatty acid degradation, fatty acid metabolism, amino acid biosynthesis, and amino acid metabolism and identified the involved critical genes (ANGPTL4, ACSBG1, CPT1A, ACADVL, PSAT1, and PHGDH). Subsequent metabolomic analysis indicated that PSNPs induced metabolic dysfunction by altering vital metabolites, mainly those of lipids (monoacylglycerols, fatty acids, sterol lipids, and glycerophospholipids) and amino acids (tyrosine, ethanolamine, and phenylalanine). Finally, integrated transcriptomic and metabolomic analysis manifested that PSNPs disrupted lipid (ether lipid, arachidonic acid, glycerophospholipid, and linoleic acid) and amino acid (phenylalanine, glycine, serine, and threonine) metabolism. In addition, the validated key genes (HMGCS2, ANGPTL4, ACSBG1, CPT1A, ACADVL, MAOA, COMT, PSAT1, and PHGDH) might contribute to PSNP-induced metabolic disorders. This study brings new perspectives to the underlying mechanism of PSNP-induced metabolic disorders in hepatocytes. It will help manage the health risk assessment of MNPs and improve public and planetary health.