Effect of the perfluorooctane sulfonamide on glucose and lipid metabolism in 3T3-L1 adipocytes and zebrafish larvae

Perfluorooctane sulfonamide (PFOSA) is an indirect source of perfluorooctane sulfonic acid (PFOS) in the environment as a precursor; however, toxicological study of PFOSA is limited. This study aimed to investigate the effects of PFOSA on glucose and lipid metabolism in 3T3-L1 adipocytes and in zebrafish larvae. 3T3-L1 adipocytes were treated with PFOSA, PFOS, and rosiglitazone (RSG) for 48 h, and assessed for cell viability, adipogenesis, glucose uptake, and regarding molecular mechanisms. PFOSA-induced alterations in lipid distribution, glucose uptake, and gene expression were further evaluated in zebrafish larvae fed normal and high-fat diet (HFD). In 3T3-L1 adipocytes, PFOSA (10 μM) and RSG (5 μM) treatment significantly increased triglyceride levels and glucose uptake, whereas PFOS (10 μM) showed no significance. The upregulated expression of Pparγ and Glut4 are involved in the observed increased glucose uptake, which was validated at protein levels. In contrast, PFOSA (0.1 and 1 μM) could reduce glucose uptake and increase fat accumulation in zebrafish larvae, which is involved in downregulation of insra and glut2. The decreased G6pase further supported disrupted glucose homeostasis, which is exacerbated by HFD. These findings showed model-specific adverse effects of PFOSA on lipid metabolism, which could be affected by the diabetic potential. Future studies should further explore biotransformation pathway of PFOSA and their potential toxicity in liver or multi-organ mimic system.