基因与营养相互作用控制白天增强剂-促进剂动态和肝脂代谢
Dishu Zhou1, Ying Chen2, Panpan Liu2
1State Key Laboratory of Cellular Stress Biology, Engineering Research Centre of Molecular Diagnostics of the Ministry of Education, National Institute for Data Science in Health and Medicine Engineering, Faculty of Medicine and Life Sciences, School of Life Sciences, Xiamen University, Xiamen 361102, Fujian, China; Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Cell metabolism
|August 26, 2025
概括
遗传变异和营养相互作用影响每日肝脏基因节奏. 雌激素相关受体玛 (ESRRγ) 在这些饮食反应代谢过程中起着关键作用,影响疾病易感性.
科学领域:
- 遗传学
- 时间生物学
- 代谢过程
背景情况:
- 生物节律是24小时的.
- 核心时钟基因之外的遗传变异对外围日间节律的影响尚不清楚.
- 了解这些相互作用对于代谢健康至关重要.
研究的目的:
- 研究遗传变异如何影响肝脏基因表达的日常模式.
- 探索遗传学,营养和肝脏新陈代谢中的日常节奏之间的相互作用.
- 确定这些节律-基因-环境相互作用的关键调节者.
主要方法:
- 在不同营养条件下对不同人类和小鼠菌株的肝脏基因表达进行比较分析.
- 动机挖掘用于确定调节节律基因表达和增强剂-促进剂相互作用 (E-PI) 的转录因子.
- 在小鼠中进行基因淘汰研究 (Esrrγ) 和在人类肝脏样本中分析单核酸多态 (SNP).
主要成果:
- 基因变异显著影响人类和小鼠的白天肝脏基因表达模式.
- 营养挑战导致肝脏基因节律的变化.
- 遗传和营养共同调节超过80%的节律基因和E-PI,ESRRγ被确定为关键调节者.
- 在小鼠中,Esrrγ 淘汰会破坏取决于饮食的代谢过程.
- 与节律基因表达相关的SNP在人体脂肪性肝脏中富含EPI,与脂质代谢特征相关.
结论:
- 遗传和环境因素,特别是营养,在控制肝脏基因表达和新陈代谢中的日间节奏方面具有动态作用.
- 雌激素相关受体玛 (ESRRγ) 是这些相互作用的关键转录因子.
- 这些发现突显了代谢特征中的基因环境相互作用的时间维度,并对与肥胖相关的疾病和个性化时间疗法产生影响.
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