Nanoplastics as potential environmental amplifiers of metabolic vulnerability: A systems perspective

Nanoplastics (NPs) are increasingly recognised as ubiquitous environmental pollutants, and evidence continues to mount that humans are exposed to NPs primarily through food and drinking water. Whilst their presence in biological systems is well documented, their role in metabolic dysfunction remains unclear. Metabolic disorders such as obesity, insulin resistance and non-alcoholic fatty liver disease are characterised by chronic inflammation, impaired energy metabolism and endocrine disruption; under these conditions, the metabolic system itself is subjected to a state of persistent stress. Existing evidence suggests that NPs may directly induce metabolic disorders. However, their impact on metabolism appears to depend heavily on host susceptibility. We therefore propose, as a working hypothesis, the 'metabolic vulnerability amplification model', which posits that NPs do not act merely as independent metabolic toxins, but may amplify pre-existing metabolic stress. In this review, we integrated evidence at the molecular, cellular and organ levels, focusing on mitochondrial dysfunction, chronic inflammation and endocrine disruption, to examine metabolic abnormalities caused by NPs at a systems level. Furthermore, we summarise emerging mitigation strategies, highlight key knowledge gaps relating to chronic low-dose exposure and in vivo dose profiling, and outline priorities for future research. Overall, this study suggests that, under specific conditions of exposure and host susceptibility, NPs may compromise metabolic resilience.