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Once ingested, nano- and microplastic particles (MNPs) can translocate from the gut to internal organs, with macrophages serving as primary targets. Kupffer cells (KCs), the liver-resident macrophages, play a central role in immune surveillance and metabolism, yet their response to MNPs remains unclear. Here, using a chronic plastic exposure model in mice, we identify KCs as the primary hepatic reservoir for MNPs. Long-term exposure alters their transcriptional profile and impairs phagocytic function, leading to metabolic dysregulation of hepatocytes. Microplastics, but not nanoplastics, reduce KC-mediated clearance of circulating cells and bacteria. Under diet-induced obesity, microplastics exacerbates hepatic lipid accumulation, while nanoplastics impair systemic glucose metabolism. Although the blood-brain barrier limits microplastic infiltration, a small fraction of ingested nanoplastics reaches the brain, where it is taken up by microglia, the brain-resident macrophages. However, we observe no signs of neuroinflammation or behavioral deficits. These findings demonstrate that chronic MNP exposure disrupts macrophage function in a size-dependent manner, with distinct consequences for liver and systemic metabolism, while the brain remains largely protected. Understanding tissue-specific vulnerabilities to MNPs is crucial for assessing their long-term health impact."}}]},{"typeName":"subject","multiple":true,"typeClass":"controlledVocabulary","value":["Medicine, Health and Life Sciences"]},{"typeName":"freeKeyword","multiple":true,"typeClass":"compound","value":[{"freeKeywordValue":{"typeName":"freeKeywordValue","multiple":false,"typeClass":"primitive","value":"nano & microplastic ingestion"}},{"freeKeywordValue":{"typeName":"freeKeywordValue","multiple":false,"typeClass":"primitive","value":"Kupffer cells"}},{"freeKeywordValue":{"typeName":"freeKeywordValue","multiple":false,"typeClass":"primitive","value":"macrophages"}},{"freeKeywordValue":{"typeName":"freeKeywordValue","multiple":false,"typeClass":"primitive","value":"liver"}},{"freeKeywordValue":{"typeName":"freeKeywordValue","multiple":false,"typeClass":"primitive","value":"high fat diet"}}]},{"typeName":"publication","multiple":true,"typeClass":"compound","value":[{"publicationRelationType":{"typeName":"publicationRelationType","multiple":false,"typeClass":"controlledVocabulary","value":"IsSupplementTo"},"publicationCitation":{"typeName":"publicationCitation","multiple":false,"typeClass":"primitive","value":"Nikola Makdissi, Maria Francesca Viola, Lisa Steinheuer et al. 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