Synergistic effects of prenatal nicotine exposure and post-weaning high-fat diet on hypercholesterolaemia in rat offspring of different sexes

Synergistic effects of prenatal nicotine exposure and post-weaning high-fat diet on hypercholesterolaemia in rat offspring of different sexes
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产前尼古丁暴露与断奶后高脂饮食对不同性别大鼠子代高胆固醇血症的协同作用

DOI:
10.1111/bcpt.13187
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发表时间:
2019
影响因子:
3.1
通讯作者:
Wang Hui
Wang Hui
中科院分区:
医学3区
文献类型:
--
作者:
Zhu Chunyan;Guo Yu;Luo Hanwen;Wu Yimeng;Magdalou Jacques;Chen Liaobin;Wang Hui

文献摘要

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高胆固醇血症被认为是一种宫内起源的疾病。最近,我们报道了产前尼古丁暴露(PNE)诱导大鼠子代出生前后总胆固醇水平异常。然而,很少有资料表明PNE后代的血清胆固醇水平存在性别差异。此外,许多先前的研究报告,血液胆固醇与日常饮食有关。本研究旨在分析PNE、高脂饮食(HFD)和性别对大鼠胆固醇代谢的相互作用。从妊娠第11天(GD)至分娩,对妊娠Wistar大鼠皮下给予2 mg/kg尼古丁。断奶后,用正常饮食或HFD喂养幼仔至24周,然后检测血清胆固醇表型和肝脏胆固醇代谢相关基因。结果表明,PNE对胆固醇表型和胆固醇代谢相关基因表现出明显的编程效应。HFD聚集了PNE诱导的成年后代高胆固醇血症,并加重了PNE后代的肝脏胆固醇代谢功能障碍。血清胆固醇水平不存在性别差异,但成年子代的胆固醇代谢基因存在PNE、HFD和性别的交互作用,表明雌性子代的胆固醇代谢更容易受到PNE和HFD的影响。总之,HFD加重了PNE诱导的高胆固醇血症,PNE或HFD处理后代的肝脏胆固醇代谢基因存在性别差异。
Hypercholesterolaemia is considered a disease with intrauterine origin. Recently, we reported that prenatal nicotine exposure (PNE) induced an abnormal level of total cholesterol in rat offspring before and after birth. However, there were little data about sex differences in serum cholesterol level in PNE offspring. In addition, many previous studies reported that blood cholesterol is associated with daily diet. This study was designed to analyse the interaction among PNE, high‐fat diet (HFD) and sex on cholesterol metabolism in the rat. Pregnant Wistar rats were administered 2 mg/kg nicotine subcutaneously from gestational day (GD) 11 until parturition. After weaning, pups were fed with normal diet or HFD till 24 weeks, and then, serum cholesterol phenotypes and hepatic cholesterol metabolism‐related genes were tested. Results showed that PNE manifested a distinct programming effect on cholesterol phenotype and cholesterol metabolism‐related genes. HFD aggregated PNE‐induced hypercholesterolaemia in adult offspring and exacerbated liver cholesterol metabolism dysfunction in PNE offspring. There was no sex difference in serum cholesterol level, but there were interactions among PNE, HFD and sex on cholesterol metabolic genes in adult offspring, which indicates that cholesterol metabolism in female offspring is more likely to be affected by PNE and HFD. In conclusion, HFD exacerbated PNE‐induced hypercholesterolaemia, and sex differences existed in liver cholesterol metabolic genes in PNE‐ or HFD‐treated offspring.