Microplastics induce insulin resistance by causing mitochondrial dysfunction associated with mROS in skeletal muscle in vitro

Microplastics pose an emerging threat to both ecological and human health. It is worth noting that muscle has proved to be the target organ of microplastic particles. Skeletal muscle is the major site of insulin-stimulated glucose disposal and subsequent glucose homeostasis and plays a key role in the regulation of glucose metabolism in the body. However, studies on the effects of microplastics on glucose metabolism and insulin sensitivity in human skeletal muscle are limited. Herein, human rhabdomyosarcoma (RD) cells were exposed to two sizes (3 μm and 100 nm) of polystyrene microplastics/nanoplastics (PS-MPs/NPs) at three concentrations (75, 150, and 300 μg/mL) to investigate the possible molecular mechanisms. Our results showed that PS-MPs/NPs could be internalized into RD cells and lead to a reduction in cellular uptake of glucose. These results suggest that PS-MPs/NPs may cause skeletal muscle insulin resistance (IR) at the cellular level. Additionally, we observed that PS-MPs/NPs not only resulted in mitochondrial damage but also induced intracellular oxidative stress. However, treatment with the mitochondria-targeted antioxidant MitoQ improved mitochondrial dysfunction and IR at the cellular level. These findings indicate that PS-MPs/NPs induce IR by causing mitochondrial dysfunction associated with mROS in skeletal muscle in vitro. The identification of these molecular mechanisms is helpful for deeply understanding of the health hazards posed by microplastics.