PFAS Exposure and Metabolic Disorders: Mechanistic Insights into Lipid and Glucose Homeostasis

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic fluorinated chemicals characterized by high environmental persistence and widespread occurrence, which have attracted increasing attention due to their potential adverse effects on human health. As the global burden of chronic diseases related to lipid and glucose dysregulation rises, identifying environmental contributors is increasingly important. Growing evidence links PFAS exposure to metabolic disorders, particularly those involving lipid and glucose metabolism. This review summarizes current findings on the mechanisms by which PFAS disrupt metabolic balance, with a focus on pathways involved in fatty acid uptake and oxidation, nuclear receptor signaling, oxidative stress, inflammation and insulin signaling. Furthermore, we highlight the convergence of molecular pathways involved in PFAS-induced lipid and glucose metabolic alterations, which may provide a mechanistic basis for understanding the development of metabolic disorders. Finally, we discuss current research limitations and future perspectives, including the potential application of computational approaches and emerging technologies to further elucidate PFAS-related metabolic effects. A comprehensive understanding of these mechanisms may help identify targets for the prevention and treatment of metabolic diseases, including obesity and type 2 diabetes, and provide regulatory policies on PFAS.