UCLA

Cardiometabolic disorders such as metabolic syndrome, obesity, diabetes, cardiovascular disease, and non-alcoholic fatty liver disease are growing public health problems across the world. Among known cardiometabolic risk factors are obesogens such as endocrine disrupting chemicals (EDCs), exogenous chemical compounds that induce endocrine and metabolic dysfunctions. To date, the species- and tissue-specific influence of EDCs on molecular programs and cardiometabolic risks has not been fully elucidated. We performed a comprehensive data-driven transcriptome-wide analysis of 44 publicly available datasets for 4 EDCs, namely Bisphenol(BPA), Bis(2-ethylhexyl) phthalate (DEHP), Tributyltin (TBT), and Perfluorooctanoic acid (PFOA), to elucidate the perturbation in genes and pathways induced by these chemicals in a species- and tissue-specific manner. Our study identified various metabolic pathways including lipid metabolism, cholesterol biosynthesis and fatty acid metabolism to be up-regulated across all chemicals and species, whereas down-regulated pathways were largely species- and tissue-specific, including immune response, cell cycle, and metabolism terms. Taken together, the genes and pathways identified highlight differential responses of the transcriptome between tissue and species and help infer the mechanisms underlying the connections between EDCs and cardiometabolic diseases.