Exposure of pregnant mice to triclosan causes hyperphagic obesity of offspring via the hypermethylation of proopiomelanocortin promoter
Exposure of pregnant mice to triclosan causes hyperphagic obesity of offspring via the hypermethylation of proopiomelanocortin promoter
复制标题
怀孕小鼠接触三氯生会通过阿黑皮素原启动子的高甲基化导致后代过度肥胖。
DOI：
10.1007/s00204-018-2338-1
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发表时间：
2019-02-01
影响因子：
6.1
通讯作者：
Chen, Ling
中科院分区：
文献类型：
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作者：
Hua, Xu;Xiong, Jian-Wei;Chen, Ling
三氯生（TCS）是一种广谱抗菌剂，广泛应用于个人护理和家庭用品中。产妇尿TCS水平与婴儿出生体重的变化有关。在本研究中，我们研究了小鼠从妊娠第6天（GD）至妊娠第14天（GD）暴露于8mg/kg TCS是否会改变雌雄后代（TCS-后代）的产前和产后生长发育以及代谢表型。与对照子代相比，雄性和雌性tcs子代出生后第1天（PND）体重下降，但出生后第5天体重增加较快。PND30和PND60 tcs后代表现出超重，内脏脂肪和脂肪细胞大小增加。PND60 tcs后代表现出延迟的葡萄糖清除和胰岛素抵抗。PND30 tcs后代的摄食量增加，但耗氧量和呼吸交换率（RER）没有变化。与对照组相比，PND30 tcs子代下丘脑弓状核（ARC）、室旁核（PVN）中促黑素细胞激素（msh）、单心1 （SIM1）的表达水平显著降低。在PND30 tcs后代中观察到POMC启动子CpG位点的高甲基化，而血清瘦素浓度升高，ARC中STAT3磷酸化水平与对照组无显著差异。本研究表明，妊娠早期/中期的TCS暴露通过POMC启动子的高甲基化降低了厌食神经肽的表达，导致出生后的肥厚性肥胖，导致成年后的代谢综合征。
Triclosan (TCS), as a broad spectrum antibacterial agent, is commonly utilized in personal care and household products. Maternal urinary TCS level has been associated with changes in birth weight of infants. We in the present study investigated whether exposure of mice to 8mg/kg TCS from gestational day (GD) 6 to GD14 alters prenatal and postnatal growth and development, and metabolic phenotypes in male and female offspring (TCS-offspring). Compared with control offspring, body weight in postnatal day (PND) 1 male or female TCS-offspring was reduced, but body weight gain was faster within postnatal 5 days. PND30 and PND60 TCS-offspring showed overweight with increases in visceral fat and adipocyte size. PND60 TCS-offspring displayed delayed glucose clearance and insulin resistance. PND30 TCS-offspring showed an increase in food intake without the changes in the oxygen consumption and respiratory exchange ratio (RER). The expression levels of proopiomelanocortin (POMC), -melanocyte-stimulating hormone (-MSH) and single-minded 1 (SIM1) in hypothalamus arcuate nucleus (ARC) and paraventricular nucleus (PVN), respectively, were significantly reduced in PND30 TCS-offspring compared to controls. The hypermethylation of CpG sites at the POMC promoter was observed in PND30 TCS-offspring, while the concentration of serum leptin was elevated and the level of STAT3 phosphorylation in ARC had no significant difference from control. This study demonstrates that TCS exposure during early/mid-gestation through the hypermethylation of the POMC promoter reduces the expression of anorexigenic neuropeptides to cause the postnatal hyperphagic obesity, leading to metabolic syndrome in adulthood.