Aged polylactic acid microplastics exacerbate lipid metabolism disorders and cardiac dysfunction via PPARγ activation in zebrafish: A comparative study with polymers and oligomers.

Polylactic acid (PLA), a biodegradable plastic, is increasingly promoted as a sustainable alternative to conventional plastics. However, its degradation under non-composting conditions and associated toxicological impacts remain insufficiently understood. This study aimed to compare the toxicity of PLA microplastics (MPs) at different degradation stages, including PLA polymers, oligomers, and aged polymers, in zebrafish larvae. Zebrafish were exposed to environmentally relevant concentrations (0.1, 1, and 10 mg/L), and morphological, biochemical, and transcriptomic analyses were performed. PLA MPs disrupted lipid metabolism, decreased ATP levels, and elevated reactive oxygen species production, ultimately leading to cardiac malformations. Mechanistically, PLA MPs activated the peroxisome proliferator-activated receptor γ (PPARγ), upregulating genes related to lipid storage and cardiac development. Co-exposure with a PPARγ antagonist GW9662 partially alleviated these effects, confirming the role of PPARγ-mediated pathways in PLA MP-induced lipid disruption and cardiotoxicity. Notably, PLA polymers showing stronger cardiac dysfunction than PLA oligomers and ultraviolet (UV)-aged PLA polymers. These findings provided critical evidence that PLA MPs impair energy homeostasis and cardiac development in zebrafish, underscoring the urgent need for comprehensive ecological risk assessments of PLA-based materials under realistic environmental conditions.