Department of Child and Adolescent Health, School of Public Health, China Medical University, Shenyang 110122, China.
Int J Environ Res Public Health. 2019 Oct 28;16(21):4152. doi: 10.3390/ijerph16214152.
The aim of this study was to investigate whether combined exposure to fructose and bisphenol A (BPA) has a synergistic effect on abnormal lipid metabolism in the liver of developmental male rats and its possible mechanism. Fifty weaned male Wistar rats were divided into five groups: the control, 13% fructose, 20% fructose, 1 µg/mL BPA, and 13% fructose + 1 µg/mL BPA (combined exposure). Rats were exposed to fructose and/or BPA through drinking water for eight weeks. Genes or proteins regulating lipid metabolism include sterol regulatory element binding protein 1 (SREBP1), adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), zinc α 2 glycoprotein (ZAG) and estrogen receptor α (ERα), and the expression of proteins regulating inflammatory response, such as TLR4 and NF-κB, were determined. Serum total cholesterol (T-CHO), triglyceride (TG), low, high density lipoprotein cholesterol (LDL-C, HDL-C), blood glucose, insulin, IL-17 and TNF-α levels were also measured. Liver tissue morphology was observed by H&E staining. The results showed that the levels of gene and protein catalyzing lipogenesis were increased (SREBP1, ACC1 and FAS), while those catalyzing lipolysis were decreased (ATGL, HSL and ZAG), accompanied by dyslipidemia, insulin resistance and hepatic fat accumulation, and there were higher expression of TLR4 and NF-κB protein and lower expression of ERα protein in liver, and increased serum IL-17 and TNF-α levels in fructose and/or BPA exposed rats compared with controls. Moreover, the above indicators were more serious in combined exposure group than in single exposure group. Therefore, abnormal lipid metabolism in the liver of developmental rats could be exacerbated by combined exposed to fructose and BPA.
本研究旨在探讨果糖和双酚 A（BPA）联合暴露是否对发育期雄性大鼠肝脏的异常脂质代谢具有协同作用及其可能的机制。将 50 只断奶雄性 Wistar 大鼠分为 5 组：对照组、13%果糖组、20%果糖组、1μg/mL BPA 组和 13%果糖+1μg/mL BPA（联合暴露组）。大鼠通过饮用水暴露于果糖和/或 BPA 中 8 周。调节脂质代谢的基因或蛋白包括固醇调节元件结合蛋白 1（SREBP1）、脂肪甘油三酯脂肪酶（ATGL）、激素敏感脂肪酶（HSL）、乙酰辅酶 A 羧化酶 1（ACC1）、脂肪酸合成酶（FAS）、锌 α2 糖蛋白（ZAG）和雌激素受体 α（ERα），并测定调节炎症反应的蛋白，如 TLR4 和 NF-κB 的表达。还测量了血清总胆固醇（T-CHO）、甘油三酯（TG）、低、高密度脂蛋白胆固醇（LDL-C、HDL-C）、血糖、胰岛素、IL-17 和 TNF-α 水平。通过 H&E 染色观察肝组织形态。结果表明，催化脂肪生成的基因和蛋白水平升高（SREBP1、ACC1 和 FAS），而催化脂肪分解的基因和蛋白水平降低（ATGL、HSL 和 ZAG），伴有血脂异常、胰岛素抵抗和肝脂肪堆积，并且在果糖和/或 BPA 暴露大鼠的肝脏中 TLR4 和 NF-κB 蛋白表达较高，ERα 蛋白表达较低，血清中 IL-17 和 TNF-α 水平升高。此外，与对照组相比，联合暴露组的上述指标更为严重。因此，果糖和 BPA 联合暴露可加重发育期大鼠肝脏的异常脂质代谢。
