Per- and Polyfluoroalkyl Substances (PFAS) as Emerging Obesogens: Mechanisms, Epidemiological Evidence, and Regulatory Challenges

The pervasive presence of per- and polyfluoroalkyl substances (PFAS) in the environment and their persistent nature raise significant concerns regarding their impact on human health. This review delves into the obesogenic potential of PFAS, shedding light on their mechanisms of action, epidemiological correlations with obesity and metabolic disorders, and the challenges faced in regulatory frameworks. PFAS, characterized by their carbon-fluorine chains, are ubiquitous in various consumer products, leading to widespread exposure through ingestion of contaminated food and water. Emerging evidence suggests that PFAS may act as endocrine-disrupting chemicals, interfering with lipid metabolism and hormone functions related to obesity. We examine in vitro, in vivo, human, and in silico studies that explore the interaction of PFAS with peroxisome proliferator-activated receptors (PPARs) and other molecular targets, influencing adipogenesis and lipid homeostasis. Furthermore, the review highlights epidemiological studies investigating the association between maternal PFAS exposure and the risk of obesity in offspring, presenting mixed and inconclusive findings that underscore the complexity of PFAS effects on human health. Presently, there are major challenges in studying PFAS toxicity, including their chemical diversity and the limitations of current regulatory guidelines, potential remediation, and detoxification. This review emphasizes the need for a multidisciplinary approach, combining advanced analytical methods, in silico models, and comprehensive epidemiological studies, to unravel the obesogenic effects of PFAS and inform effective public health strategies.