Objective: Hexafluoropropylene oxide dimer acid (HFPO-DA), also known as GenX, is widely used globally, raising concerns about its safety and public health implications. However, its toxicity mechanism remains unclear. The purpose of this study was to develop a reliable method for detecting HFPO-DA in mice and to investigate its absorption, distribution, and impact on hepatic lipid metabolism. Method: HFPO-DA levels were measured in the serum and eight tissues of C57BL/6J mice after oral administration using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Lipid metabolites in the liver were also detected and analyzed. Results: HFPO-DA was rapidly absorbed into the bloodstream and widely distributed throughout all tested tissues. It penetrated the blood–brain barrier, with the highest concentration in the liver; however, long-term effects on the lungs also warrant attention. HFPO-DA disrupted liver lipid metabolism, leading to acylcarnitine accumulation while lowering triglycerides and cholesterol. Conclusion: This study on the pharmacokinetics and tissue distribution of HFPO-DA in mice following oral exposure revealed that HFPO-DA exacerbates liver injury by altering hepatic lipid metabolism. These findings provide theoretical support for toxicological studies on the emerging environmental pollutant HFPO-DA.

The acute gouty arthritis (AGA) to chronic gouty arthritis (CGA) transition is a critical phase leading to irreversible joint damage and systemic complications. However, current molecular mechanism investigations have remained limited to single-omics approaches that lack comprehensive multi-omics explorations. We integrate high-depth data-independent acquisition (DIA) proteomics and untargeted metabolomics to analyze serum samples from healthy controls (n =28), AGA (n = 31), and CGA (n = 14) patients to address this gap. Through differential expression analysis, we identified nine persistently dysregulated pivotal proteins with robust discriminative capacity, including the urate excretion regulator ZBTB20 and inflammation/immune-related proteins (GUCY1A2, CNDP1, LYZ, SERPINA5, GSN). Additionally, 11 consistently altered core metabolites with diagnostic potential were detected, indicating perturbations in sex hormones, thyroid hormones, gut microbiota-derived metabolites, environmental exposures, and nutritional factors. Multi-omics KEGG enrichment analysis highlighted thyroid hormone synthesis, AMPK signaling pathway, and taurine and hypotaurine metabolism as central pathways. Correlation network analysis further revealed significant immune dysregulation, illustrating an evolution from acute immune activation to chronic inflammation during AGA-to-CGA progression. Our study establishes that a coordinated disruption of the thyroid hormone–AMPK–taurine metabolic axis and concomitant immune microenvironment remodeling is associated with chronic gout development. These findings provide critical targets for developing early diagnostic indicators and targeted interventions for CGA.