Background: Dimethylformamide (DMF) is a widely used organic solvent in chemical synthesis, pharmaceuticals, and electronics. Exposure to DMF has been associated with neurocognitive impairments and biological aging, which may contribute to the development of metabolic diseases. However, systematic studies on DMF-mediated metabolic diseases are limited. This study utilized network toxicology and molecular docking to explore how DMF may cause metabolic diseases, focusing on cellular senescence, lipid and atherosclerosis, Alzheimer’s disease (AD), and type II diabetes mellitus. Methods: We identified potential targets of DMF using PubChem, SwissADME, and GeneCards, and analyzed core targets related to metabolic disease with STRING analysis and Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to assess target functions. We also evaluated the binding affinity of DMF to these targets through molecular docking using AutoDock Vina and PyMOL. Results: We identified 106 potential targets shared between DMF and metabolic diseases, and further examined 28 core targets (e.g., MAPK3, MAPK1, and CYP2C9). GO and KEGG analyses indicated that DMF may contribute to metabolic diseases by disrupting mitochondrial function, affecting energy metabolic processes, altering redox homeostasis, and interfering with TGF-β and MAPK signaling pathways. Notably, the MAPK family pathways were enriched across all four conditions, indicating their critical role. Molecular docking revealed stable binding of DMF to relevant target proteins associated with the condition. Key proteins included CYP2C9, MAPK3, MMP9, MAPK1, CASP1, and MAPK14, with binding energies ranging from −3.4 to −2.2 kcal/mol. In AD, PTGS2, GSK3B, MAPK3, and MAPK1 exhibited binding energies between −3.4 and −2.6 kcal/mol. For type II diabetes, MAPK3 and MAPK1 showed binding energies from −3.4 to −2.8 kcal/mol, while for cellular senescence pathways, MAPK3, MAPK1, and MAPK14 had binding energies ranging from −3.4 to −2.6 kcal/mol. Conclusion: DMF may promote metabolic diseases by disrupting mitochondrial function, impairing energy metabolism, and damaging tissues and cells involved in metabolic regulation. This study provided valuable insights into how environmental pollutants like DMF can trigger human metabolic diseases and emphasized the interconnections among these related conditions, providing a foundation for future prevention and treatment strategies.
Gao et al. (Fri,) studied this question.