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 (Mrps12 and Mrpl53), cell differentiation (Bbc3, Lrrc15 and Gdf15), lipid catabolism (Etnppl and lipg) and tRNA methyltransferase (Trmt112), 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.