Environmental chemicals, such as plasticizers, have been linked to increased rates of obesity, according to epidemiological studies. Acetyl triethyl citrate (ATEC) is a plasticizer that is commonly utilized in pharmaceutical products and food packaging as a non-phthalate alternative. Due to its direct contact with the human body and high leakage rate from the polymers, assessment of the potential risk of ATEC exposure at environmentally relevant low doses to human health is needed. Male C57BL/6 J mice were fed diets containing ATEC at doses of either 0.1 or 10 μg/kg per day in a period of 12 weeks to mimic the real exposure environment.  The findings suggest that in C57BL/6 J mice, ATEC exposure resulted in increased body weight gain, body fat percentage, and benign hepatocytes, as well as adipocyte size.  Consistent with in vivo models, ATEC treatment obviously stimulated the increase of intracellular lipid load in both mouse and human hepatocytes. Mechanically, ATEC induced the transcriptional expression of genes involved in de novo lipogenesis and lipid uptake. Using both enzyme inhibitor and small interfering RNA (siRNA) transfection, we found that stearoyl-coenzyme A desaturase 1 (SCD1) played a significant role in ATEC-induced intracellular lipid accumulation. This study for the first time provided initial evidence suggesting the obesogenic and fatty liver-inducing effect of ATEC at low doses near human exposure levels, and ATEC might be a potential environmental obesogen and its effect on human health need to be further evaluated.

根据流行病学研究，增塑剂等环境化学物质与肥胖率增加有关。乙酰柠檬酸三乙酯 (ATEC) 是一种增塑剂，通常作为非邻苯二甲酸酯替代品用于医药产品和食品包装。由于其与人体直接接触且聚合物的泄漏率较高，因此需要评估环境相关低剂量下 ATEC 暴露对人类健康的潜在风险。雄性 C57BL/6 J 小鼠在 12 周内每天喂食含有 ATEC 的饮食，剂量为 0.1 或 10 μg/kg，以模拟真实的暴露环境。研究结果表明，在 C57BL/6 J 小鼠中，ATEC 暴露导致体重增加、体脂百分比、良性肝细胞以及脂肪细胞大小增加。与体内模型一致，ATEC 治疗明显刺激小鼠和人肝细胞细胞内脂质负荷的增加。从机械角度来看，ATEC 诱导参与脂肪从头生成和脂质摄取的基因的转录表达。使用酶抑制剂和小干扰 RNA (siRNA) 转染，我们发现硬脂酰辅酶 A 去饱和酶 1 (SCD1) 在 ATEC 诱导的细胞内脂质积累中发挥重要作用。该研究首次提供了初步证据表明ATEC在接近人类暴露水平的低剂量下具有致肥胖和脂肪肝诱导作用，ATEC可能是一种潜在的环境致肥胖剂，其对人类健康的影响有待进一步评估。