Mixtures of polystyrene micro and nanoplastics affects fat and glucose metabolism in 3T3-L1 adipocytes and zebrafish larvae

Microplastics (MPs) and nanoplastics (NPs) are pervasive pollutants that pose a hazard to human health. Although most previous studies have investigated the effects of MPs and NPs on digestion, oxidative stress, and inflammation in diverse models, the combined effect of plastic mixtures (PM) containing MPs and NPs on obesity and type 2 diabetes mellitus (T2DM) remains unknown. The hypothesis of our study is to verify the association between PM exposure and clinical features of metabolic diseases such as lipogenesis and insulin resistance. Therefore, we investigated the effects of PM on fat and glucose metabolism in 3T3-L1 cells and high-fat diet (HFD)-induced zebrafish larvae. PM exposure increased cell viability, differentiation, adipogenesis (PPARγ and C/EBPα), and lipogenesis (FAS and SREBP-1c), while it decreased glucose uptake and inhibited insulin signal (IRS1, PI3K, AKT, and GLUT4) expression 3T3-L1 cells. In zebrafish larvae, PM mainly bioaccumulated in the intestine and pancreatic tissue, reducing glucose uptake and increasing body weight and blood glucose compared to controls. Moreover, PM significantly increased adipogenic differentiation (PPARγ) and synthesis (FASN and FABP), proinflammatory cytokines (TNF-α and IL-6), and gluconeogenesis (PCK1 and G6Pase). Conversely, energy and fat metabolism (AMPKα and adiponectin), insulin production (INSα), signaling pathway (IRS1, AKT, and GLUT2), and anti-inflammatory cytokines (IL-10 and IL-4) were suppressed. Overall, this study sheds light on the mechanisms responsible for the detrimental effects of PM exposure on fat and glucose metabolism, providing insights into metabolic disorders, like type 2 diabetes, in both in vitro and in vivo models.