Increased adiposity, inflammation, metabolic disruption and dyslipidemia in adult male offspring of DOSS treated C57BL/6 dams

Abstract

Evidence indicates that obesity can be promoted by chemical ‘obesogens’ that drive adiposity, hunger, inflammation and suppress metabolism. Dioctyl sodium sulfosuccinate (DOSS), a lipid emulsifier and candidate obesogen in vitro, is widely used in processed foods, cosmetics and as stool softener medicines commonly used during pregnancy. In vivo testing of DOSS was performed in a developmental origins of adult obesity model. Pregnant mice were orally administered vehicle control or DOSS at times and doses comparable to stool softener use during human pregnancy. All weaned offspring consumed only standard diet. Adult male but not female offspring of DOSS-treated dams showed significantly increased body mass, overall and visceral fat masses, and decreased bone area. They exhibited significant decreases in plasma adiponectin and increases in leptin, glucose intolerance and hyperinsulinemia. Inflammatory IL-6 was elevated, as was adipose Cox2 and Nox4 gene expressions, which may be associated with promoter DNA methylation changes. Multiple significant phospholipid/sterol lipid increases paralleled profiles from long-term high-fat diet induced obesity in males. Collectively, developmental DOSS exposure leads to increased adult adiposity, inflammation, metabolic disorder and dyslipidemia in offspring fed a standard diet, suggesting that pharmaceutical and other sources of DOSS taken during human pregnancy might contribute to long-term obesity-related health concerns in offspring.