Molecular and Cellular Biology and Pathobiology Program, Medical University of South Carolina, Charleston, SC, USA.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.
Sci Rep. 2019 Feb 6;9(1):1530. doi: 10.1038/s41598-018-38383-9.
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.
有证据表明，化学“肥胖因子”会促进肥胖、饥饿、炎症并抑制新陈代谢，从而导致肥胖。二辛基琥珀酸磺酸钠（DOSS）是一种脂类乳化剂，也是体外研究的肥胖因子候选物，广泛用于加工食品、化妆品和作为通便药物，这些药物在怀孕期间也常用。本研究在成年肥胖的发育起源模型中对 DOSS 进行了体内测试。在与人类怀孕期间使用通便药物相当的时间和剂量下，给怀孕的老鼠口服给予载体对照或 DOSS。所有断奶的后代仅食用标准饮食。与 DOSS 处理的母鼠的雄性而非雌性后代相比，其体重、总体和内脏脂肪质量显著增加，骨面积减少。它们的血浆脂联素降低，瘦素增加，葡萄糖耐量降低和高胰岛素血症。促炎细胞因子 IL-6 升高，脂肪组织 Cox2 和 Nox4 基因表达增加，这可能与启动子 DNA 甲基化变化有关。与长期高脂肪饮食诱导的肥胖雄性相比，多种显著的磷脂/固醇脂质增加与 DOSS 暴露相关。总之，发育性 DOSS 暴露导致后代在食用标准饮食时出现成年肥胖、炎症、代谢紊乱和血脂异常，这表明怀孕期间服用的药物和其他来源的 DOSS 可能会导致后代长期肥胖相关的健康问题。
