Investigation of steatosis profiles induced by pesticides using liver organ-on-chip model and omics analysis

Several studies have reported a correlation between pesticides exposure and metabolic disorders. Dichlorodiphenyltrichloroethane (DDT) permethrin (PMT), two highly prevalent in the environment, been associated to dysregulation of liver lipids glucose metabolisms non-alcoholic fatty disease (NAFLD). However, effects DDT/PMT mixtures mechanisms mediating their action remain unclear. Here, we used multi-omic investigate damage induced by DDT, PMT mixture rat organ-on-chip. Organ-on-chip allow reproduction vivo-like micro-environment. Two concentrations, 15 150 ?M, were expose hepatocytes for 24 h under perfusion. The transcriptome metabolome analysis suggested dose-dependent effect all conditions, with profile close control low-doses. comparison high-doses detected 266/24, 256/24 1349/30 genes/metabolites differentially expressed DDT150, PMT150 Mix150 (DDT150/PMT150). Transcriptome modulation reflected inflammation, steatosis, necrosis, PPAR signaling acid metabolism. highlighted common signature three treatments including lipid carbohydrates production, decrease amino acids krebs cycle intermediates. Our study illustrates potential organ-on-chip coupled multi-omics toxicological provides new tools chemical risk assessment.