由VCD诱导的绝经小鼠模型揭示了肝脏新陈代谢的重编程
bioRxiv : the preprint server for biology
|January 3, 2024
概括
更年期会增加代谢疾病的风险. 这项研究表明,小鼠的更年期模型恶化了肝脏脂肪积累和肥胖易感性,特别是在高脂肪饮食中.
科学领域:
- 生殖生物学 生殖生物学
- 代谢性疾病 代谢性疾病
- 线粒体生物学 线粒体生物学
背景情况:
- 更年期会对能量代谢产生负面影响,并增加患肝硬化等代谢疾病的风险.
- 连接更年期与代谢功能障碍的潜在机制仍然不太清楚.
- 乙烯基环二氧化物 (VCD) 用于诱导卵巢卵泡缩,创建更年期的小鼠模型.
研究的目的:
- 调查VCD诱导的更年期模型对身体组成,能量消耗,肝脏线粒体功能和肝脏肥胖症的影响.
- 在不同的饮食条件下检查这些影响,包括低脂肪和高脂肪,高糖饮食.
- 阐明更年期影响代谢健康和疾病易感性的机制.
主要方法:
- 雌性C57BL6/J小鼠接受了VCD治疗,以诱导类似更年期的表型.
- 小鼠接受了低脂肪饮食 (LFD) 或长期高脂肪,高糖饮食 (HFHS) 16 周.
- 评估身体组成,能量消耗,肝脏线粒体呼吸和肝脏脂肪.
- 进行了肝脏RNA测序,以分析脂质和胆固醇合成途径中的基因表达变化.
主要成果:
- VCD治疗成功诱导了与卵巢卵泡损失和FSH水平升高的更年期状况.
- VCD小鼠在LFD或短期HFHS上没有显示身体组成或能量消耗的变化.
- 慢性HFHS饮食显著增加了VCD小鼠的体重增加,脂肪质量和肝肥胖症,与对照组相比.
- VCD小鼠在LFD上表现出抑制的肝脏线粒体呼吸,在慢性HFHS下补偿性增加.
- VCD 治疗提高了肝脂和胆固醇合成途径的调节.
结论:
- 由VCD诱导的更年期模型损害了肝脏线粒体功能和脂质/胆固醇平衡.
- 这种受损的状态增加了对饮食诱导的肝硬化和肥胖的易感性.
- 了解这些机制对于开发治疗绝经后妇女代谢疾病的干预措施至关重要.
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