Lipid metabolism disorders associated with dioxin exposure in a cohort of Chinese male workers revealed by a comprehensive lipidomics study

•Dioxin exposure closely associated with lipid changes in humans.•TG accumulation related to dioxin exposure was observed.•Sphingolipid changes associated with inflammation and apoptosis were found.•GP remodeling suggested the impacts of dioxins on cell homeostasis.•Imbalanced FFA metabolism was found to be associated with dioxin exposure. Dioxins, environmentally stable and ubiquitous, have been found to induce metabolic changes especially in lipids and be related to multiple diseases. However, limited study is available on lipid alternations related to human exposure to dioxins. This study aims to explore the serum lipidomic characterization and to understand the underlying mechanisms of adverse health risks associated with dioxin exposure. A lipidomic study integrating nontargeted lipidomics, and targeted free fatty acid (FFA) and acyl-coenzyme A (acyl-CoA) analyses were conducted to investigate the 94 serum samples from two groups of male workers with remarkably different dioxin concentrations. The obtained results exhibited distinct lipidomic signatures between the high and low exposed groups. A total of 37 lipids were identified with the significant changes. The results revealed that dioxin exposure caused accumulations of triglyceride (TG), ceramide (Cer) and sphingoid (So), remodeling of glycerophospholipid (GP), imbalanced FFA metabolism, as well as upregulation of platelet-activating factor (PAF). These findings implied the associations between dioxin exposure and potential adverse health risks including inflammation, apoptosis, cardiovascular diseases (CVDs), and liver diseases. This study is the first to explain the associations between dioxin exposure and health effects at the level of lipid metabolism.