A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring
A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring
复制标题
孕前母亲肥胖小鼠模型与后代暴露于高脂肪饮食导致雄性后代认知障碍
DOI：
10.1016/j.yexcr.2018.04.019
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发表时间：
2018
影响因子：
3.7
通讯作者：
Zhang Hua
中科院分区：
文献类型：
--
作者：
Zhu Chen;Han Ting-Li;Zhao Yalan;Zhou Xiaobo;Mao Xun;Qi Hongbo;Baker Philip N.;Zhang Hua
研究背景认知功能障碍（cognitive impairment，cardiac impairment）是一种以注意力、工作记忆和执行功能障碍为特征的脑功能障碍。母亲肥胖和后代高脂饮食（HFD）的消费已被认为通过其对海马和前额叶皮质的影响对后代的认知功能产生有害后果。因此，我们的研究旨在探讨母体肥胖和后代HFD暴露对后代脑代谢组的影响。MethodsIn我们的试点研究中，LepRdb/+小鼠模型被用来模拟孕前母体肥胖和c57 bl/6野生型被用作对照组。后代在断奶后（8至10周）喂食HFD或低脂对照饮食（LFD）。在28至30周之间进行镜子水迷宫以测量认知功能。使用气相色谱-质谱联用仪分析了在30-32周的前额叶皮层和海马从后代的脂肪酸代谢谱。ResultsThe记忆的雄性后代从肥胖的母鼠，消耗HFD断奶后，显着受损时相比，控制后代小鼠。在雌性后代中未观察到显著差异。在雄性小鼠中，前额叶皮质中的脂肪酸代谢物受母体肥胖的影响最大，而海马中的脂肪酸代谢物受后代饮食的影响最大。十六烷酸和十八烷酸显着影响在海马和前额叶皮层，作为一个结果的母亲肥胖和HFD的后代。ConclusionOur研究结果表明，母亲肥胖和HFD的后代相结合，可能会导致空间认知缺陷的男性后代，通过影响前额叶皮层和海马的脂肪酸代谢产物。需要进一步的研究来验证我们的试点研究结果。
BackgroundCognitive impairment is a brain dysfunction characterized by neuropsychological deficits in attention, working memory, and executive function. Maternal obesity and consumption of a high-fat diet (HFD) in the offspring has been suggested to have detrimental consequences for offspring cognitive function through its effect on the hippocampus and prefrontal cortex. Therefore, our study aimed to investigate the effects of maternal obesity and offspring HFD exposure on the brain metabolome of the offspring.MethodsIn our pilot study, a LepRdb/+ mouse model was used to model pre-pregnancy maternal obesity and the c57bl/6 wildtype was used as a control group. Offspring were fed either a HFD or a low-fat control diet (LFD) after weaning (between 8 and 10 weeks). The Mirrors water maze was performed between 28 and 30 weeks to measure cognitive function. Fatty acid metabolomic profiles of the prefrontal cortex and hippocampus from the offspring at 30–32 weeks were analyzed using gas chromatography-mass spectrometry.ResultsThe memory of male offspring from obese maternal mice, consuming a HFD post-weaning, was significantly impaired when compared to the control offspring mice. No significant differences were observed in female offspring. In male mice, the fatty acid metabolites in the prefrontal cortex were most affected by maternal obesity, whereas, the fatty acid metabolites in the hippocampus were most affected by the offspring's diet. Hexadecanoic acid and octadecanoic acid were significantly affected in both the hippocampus and pre-frontal cortex, as a result of maternal obesity and a HFD in the offspring.ConclusionOur findings suggest that the combination of maternal obesity and HFD in the offspring can result in spatial cognitive deficiency in the male offspring, by influencing the fatty acid metabolite profiles in the prefrontal cortex and hippocampus. Further research is needed to validate the results of our pilot study.