Lipidomics Approaches Reveal Tissue-Specific Lipidome Remodeling Induced by Micro- and Nanoplastic Exposure

Micro- and nanoplastics (MNPs) are increasingly recognized as frequent environmental pollutants with growing evidence of tissue-specific lipid disruption in exposed organisms. MNP exposure is unavoidable and has attracted global attention due to its potential public health and ecological security risks. Unlike earlier studies that emphasize oxidative stress and inflammation, recent findings show that lipids are among the earliest and most sensitive molecular targets of MNP exposure. Lipidomics investigations across animal models reveal consistent patterns of lipidome remodeling, including altered phospholipid composition, disrupted sphingolipid balance, increased neutral-lipid storage, and mitochondrial lipid damage in metabolically active tissues such as the liver, kidney, lung, adipose tissue, and brain. Mechanistically, MNPs perturb membrane bilayer organization, induce MUFA and PUFA peroxidation, and destabilize lysosomal and mitochondrial function. These alterations trigger cardiolipin oxidation, ceramide accumulation, lipid droplet biogenesis, and impaired lipophagy, which collectively promote metabolic stress, energy imbalance, and neurotoxic or hepatotoxic phenotypes. Despite the growing number of tissue-specific studies, a major gap remains in understanding systemic MNP toxicity. The present review uniquely emphasizes tissue-resolved lipidomic signatures to identify convergent pathways of lipid disruption and proposes a conceptual framework, the “Lipid–Stress Axis”, to explain how localized lipidome perturbations may propagate into broader physiological dysfunction. By integrating lipidomics with metabolomics, imaging, and systems-biology approaches, we highlight key lipid-based biomarkers, mechanistic insights, and research needs essential for improving risk assessment and developing mitigation strategies against MNP-induced lipid dysregulation.