Molecular Landscape Remodeling Unravels the Cross-Links of Microplastics-Induced Lipidomic Fluctuations, Nutrient Disorders and Energy Disarrangements

Microplastics are emerging contaminants that pose health risks. They can cause hepatic lipid interventions, but the underlying mechanisms require investigation. This study assessed the retention of polypropylene microplastics in mouse liver and determined the intercorrelations between hepatic lipid fluctuations and transcriptomic changes. Microplastic-induced liver dysfunction was confirmed by the variations of transamination, cholesterol metabolism, biotransformation, and redox state. Chronic high-dose treatment induced distinct pathological changes, including regional fibrotic remodeling and ultrastructural mitochondrial abnormalities. Raman biospectra of liver slice proposed vital peaks of 1060, 1132, 1168, 1340, 1446, 1618, and 1670 cm^-1, representing the liver biomolecule landscapes. Transcriptomic changes were mainly involved in mRNA transcription, multicellular organism development, various stimuli response, cell differentiation, and lipid metabolic process. Microplastic exposure dosage exerted more profound effects than exposure duration on gene expressions of oxidation-reduction process, signal transduction, and lipid metabolism. WGCNA analysis proposed 47 hub genes involved gene expression orchestration, cell fate monitor, and mitochondria translation modulation. Nine differentially expressed genes associated with lipid biomarkers were related to mitochondria transcription (<i>Mrps12</i> and <i>Mrpl53</i>), cell differentiation <i>(Bbc3</i>, <i>Lrrc15</i> and <i>Gdf15</i>), lipid catabolism (<i>Etnppl</i> and <i>lipg</i>) and tRNA methyltransferase (<i>Trmt112</i>), and Raman peak at 1670 cm^-1 intimately connected with aggregated forms of protein. Our findings suggested that polypropylene microplastics could change the liver molecular landscape and induce lipid metabolism disorders and transcriptomic changes in mitochondrial protein translation and expression regulation, highlighting their significant consequences in nutrient and energy imbalance.