College of Life Science, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
College of Environment, Zhejiang University of Technology, Hangzhou, 310032, China.
Environ Pollut. 2019 Jan;244:657-666. doi: 10.1016/j.envpol.2018.08.091. Epub 2018 Sep 20.
Metabolic disturbance is the prerequisite to developing metabolic disease. An increasing number of reports have shown that exposure to environmental endocrine-disrupting chemicals (EDCs) can cause metabolic syndrome and may be related to metabolic disease. However, the potential mechanism of EDC-related lipid metabolism disruption in the endocrine organs (especially gut microbiome) during pubertal exposure remains elusive at the body burden level. We observed that male mice fed with 0.05 mg/kg b.w. MEHP under a high-fat diet caused enhancement in the fat mass, total cholesterol, high- and low-density lipoprotein cholesterol. MEHP intake induced a significant shift in microbiota composition, including the relative abundance of Firmicutes and reduction of Verrucomicrobia. Statistical analysis showed a positive correlation between several bacterial taxa and cholesterol body burden. Also, MEHP intake induced adipocyte hypertrophy and cholesterol overloading, which sense cholesterol synthesis genes such as Srebp2 and Hmgcr. That caused adipocyte dysfunction. Finally, cholesterol deposition and transportation was imbalance in the mice liver. Conclusively, by targeting the endocrine organs, EDCs would increase the risk of cholesterol burden even at a low concentration when coupled with a high-fat diet during pubertal period in male mice.
代谢紊乱是代谢性疾病发生的前提。越来越多的报道表明，暴露于环境内分泌干扰化学物质（EDCs）会导致代谢综合征，并可能与代谢性疾病有关。然而，在青春期接触时，内分泌器官（特别是肠道微生物组）中 EDC 相关脂质代谢紊乱的潜在机制在机体负担水平上仍不清楚。我们观察到，高脂肪饮食下雄性小鼠摄入 0.05mg/kg bw MEHP 会导致脂肪量、总胆固醇、高和低密脂蛋白胆固醇增加。MEHP 的摄入导致微生物群落组成发生显著变化，包括厚壁菌门的相对丰度增加和疣微菌门的减少。统计分析显示，几种细菌类群与胆固醇体负荷之间存在正相关。此外，MEHP 的摄入诱导脂肪细胞肥大和胆固醇过载，从而感知胆固醇合成基因如 Srebp2 和 Hmgcr。这导致脂肪细胞功能障碍。最后，在小鼠肝脏中胆固醇的沉积和运输失去平衡。总之，通过靶向内分泌器官，EDCs 即使在青春期与高脂肪饮食结合时以低浓度存在，也会增加胆固醇负担的风险。
