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一个白天血清脂质整合肝脏脂质生成和周围脂肪酸的使用
Sihao Liu1, Jonathan D Brown, Kristopher J Stanya
11] Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA [2].
Nature
|October 25, 2013
概括
研究人员发现了一条新的途径,通过特定的脂质PC{18:0/18:1},肝脏PPARδ通过肌肉控制脂肪的使用. 这一发现将肝脂生成与肌肉能量使用联系起来,并可能影响肥胖等代谢障碍.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 循环节律是指循环节律的节奏.
- 脂质代谢 脂质的代谢
背景情况:
- 肝脏de novo脂质生成将葡萄糖转化为脂肪,遵循昼夜节律,并受到Rev-erbα/β等因素的调节.
- 肝脏脂质生成中断与全身代谢问题有关,这表明器官间的通信.
研究的目的:
- 在黑暗周期期间识别节律性脂质合成的转录激活剂.
- 阐明肝脏在与外围组织进行能量恒温的沟通中的作用.
- 定义一种依赖PPARδ的途径,将肝脂生与肌肉脂肪利用联系起来.
主要方法:
- 研究了PPARδ在肝脏中昼间脂原基因表达中的作用.
- 在小鼠中利用肝脏特定的PPARδ激活和肝细胞-Ppard删除模型.
- 采用无偏见的代谢物分析来识别关键的循环脂质.
- 在饮食诱导的肥胖和db/db小鼠模型中使用PC{18:0/18:1}.
主要成果:
- 在养期间,PPARδ控制肝脂原基因的白天表达.
- 肝脏的PPARδ激活增强了肌肉脂肪酸的吸收;它的删除减少了它.
- 鉴定了类胆18:0/18:1 (PC(18:0/18:1)) 作为一种通过昼间肝脏PPARδ调节的血清脂质.
- PC(18:0/18:1) 降低食后脂质,并通过PPARα增加肌肉脂肪酸的使用.
- 高脂肪食扰乱了节奏PC的产生;施用改善了db/db小鼠的代谢平衡.
结论:
- 肝脏中的PPARδ-PC(18:0/18:1) 信号轴调节肌肉脂质利用.
- 这一途径将肝脂质合成与外围能量消耗相结合.
- 这种日间信号的失调可能会导致肥胖等代谢障碍.
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