Effects of Perinatal Exposure to Dibutyltin Chloride on Fat and Glucose Metabolism in Mice, and Molecular Mechanisms, in Vitro

Background: The organotin dibutyltin (DBT) is used in the manufacture of polyvinyl chloride (PVC) plastics, in construction materials, and in medical devices. Previous animal studies showed detrimental effects of DBT during in utero development at relatively high doses, but little was known about the effects of DBT exposure at environmentally relevant doses on endpoints such as obesity and metabolic disease. Objectives: We tested the potential obesogenic effects of DBT using in vitro and in vivo models. Methods. We evaluated the effects of DBT on nuclear receptor activation and adipogenic potential using human and mouse multipotent mesenchymal stromal stem cells (MSCs). We also evaluated the effects of perinatal exposure to environmentally relevant doses of DBT in C57BL/6J mice. Results: DBT activated human and mouse PPARγ and RXRα in transient transfection assays, increased expression of adipogenic genes, promoted adipogenic differentiation and increased lipid accumulation in mouse and human MSCs, in vit...