School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563003, P.R. China.
Department of Hospital Infection and Control, The First People's Hospital of Guiyang city, Guiyang, Guizhou, 550002, P.R. China.
Sci Rep. 2018 Feb 19;8(1):3232. doi: 10.1038/s41598-018-21725-y.
Exposure to environmental endocrine disruptors (EEDs) contributes to the pathogenesis of many metabolic disorders. Here, we have analyzed the effect of the EED-nonylphenol (NP) on the promotion of non-alcoholic fatty liver disease (NAFLD) in rats fed high sucrose-high fat diet (HSHFD). Fifty Sprague-Dawley rats were divided into five groups: controls fed a normal diet (C-ND); HSHFD-fed controls (C-HSHFD); and rats fed a HSHFD combined with NP at doses of 0.02 μg/kg/day (NP-L-HSHFD), 0.2 μg/kg/day (NP-M-HSHFD), and 2 μg/kg/day (NP-H-HSHFD). Subchronic exposure to NP coupled with HSHFD increased daily water and food intake (p < 0.05), hepatic echogenicity and oblique liver diameter (p < 0.05), and plasma levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, and low density lipoprotein cholesterol (p < 0.05). Combined exposure to NP and HSHFD induced macrovesicular steatosis with dilation and congestion of the central vein, liver inflammatory cell infiltration, and expression of genes regulating lipid metabolism, SREBP-1C, FAS, and Ucp2. These results demonstrate that NP aggravates NAFLD in HSHFD-treated rats by up-regulating lipogenic genes, and that HSHFD increases the toxic effects of NP. Thus subchronic NP exposure may lead to NAFLD, especially when combined with a high-sucrose/high-fat diet.
暴露于环境内分泌干扰物（EEDs）会导致许多代谢紊乱的发病机制。在这里，我们分析了 EED-壬基酚（NP）对高蔗糖高脂肪饮食（HSHFD）喂养大鼠非酒精性脂肪肝病（NAFLD）促进作用的影响。将 50 只 Sprague-Dawley 大鼠分为五组：正常饮食喂养对照组（C-ND）；HSHFD 喂养对照组（C-HSHFD）；以及分别用 0.02μg/kg/天（NP-L-HSHFD）、0.2μg/kg/天（NP-M-HSHFD）和 2μg/kg/天（NP-H-HSHFD）NP 处理的 HSHFD 喂养大鼠。亚慢性 NP 暴露与 HSHFD 联合作用增加了大鼠每日的水和食物摄入量（p<0.05）、肝脏回声和斜径（p<0.05）以及丙氨酸转氨酶、天冬氨酸转氨酶、总胆固醇、甘油三酯和低密度脂蛋白胆固醇的血浆水平（p<0.05）。NP 与 HSHFD 的联合暴露诱导了大泡性脂肪变性，伴有中央静脉扩张和充血、肝炎性细胞浸润以及调节脂质代谢的基因 SREBP-1C、FAS 和 Ucp2 的表达。这些结果表明，NP 通过上调生脂基因加重了 HSHFD 处理大鼠的 NAFLD，并且 HSHFD 增加了 NP 的毒性作用。因此，亚慢性 NP 暴露可能导致 NAFLD，尤其是与高蔗糖/高脂肪饮食联合作用时。
