肥胖会影响大脑皮层基因表达的APOE基因型和性别依赖的方式
Harshul Pandit1, Nahdia S Jones1, G William Rebeck2
1Department of Neuroscience, Georgetown University Medical Center, 3970 Reservoir Road N.W., Washington, DC, 20007, USA.
International journal of obesity (2005)
|March 7, 2024
概括
高脂肪饮食 (HFD) 肥胖影响雌性小鼠的大脑比雄性更大,APOE3显示出比APOE4更大的转录组变化. 这表明APOE4大脑可能更容易受到与肥胖相关的压力和阿尔茨海默病的影响.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 肥胖是阿尔茨海默病 (AD) 的一个显著可修改的风险因素.
- 饮食,阿波利波蛋白E (APOE) 基因型和性别对与肥胖相关的大脑变化的影响尚未完全理解.
研究的目的:
- 为了研究高脂肪饮食 (HFD) 诱导的肥胖对大脑转录学的影响.
- 在小鼠模型中检查HFD,APOE基因型 (APOE3和APOE4) 和性别之间的相互作用.
主要方法:
- 在4个月的时间里,APOE3和APOE4敲入小鼠被食HFD或对照食.
- 在大脑皮层样本上进行RNA测序,以分析基因表达变化.
主要成果:
- 雌性小鼠表现出大量的HFD诱导的转录基因变化,与雄性不同.
- 与APOE4雌性小鼠 (90个基因) 相比,APOE3雌性小鼠显示出显著更多的基因表达变化 (506个基因).
- 在APOE3小鼠中,HFD影响了与食行为,血液循环,昼夜节律,细胞外基质和细胞粘附相关的皮质路径.
结论:
- 雌性小鼠和APOE3基因型对HFD表现出最明显的转录基因反应,特别是在养行为和细胞外矩阵重塑途径方面.
- 在APOE4大脑中对与肥胖相关的压力的有限反应可能会增加对与年龄有关的和AD相关的神经疾病的敏感性.
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