一个依赖激素的模块,调节能量平衡
Biao Wang1, Noel Moya, Sherry Niessen
1Peptide Biology Laboratories, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Cell
|May 14, 2011
概括
科学家们发现了一种新的荷尔蒙调节途径,涉及SIK3和HDAC4,可以控制禁食期间的能量平衡. 这条通路与SIRT1通路一起工作,以管理脂肪和葡萄糖代谢.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子内分泌学分子内分泌学
- 多虫的遗传学 多虫的遗传学
背景情况:
- 转生动物在禁食期间转向燃烧脂肪,以保持能量平衡.
- SIRT1 deacetylates FOXO 在压力和营养缺乏下促进代谢基因表达.
- 对于FOXO脱乙的荷尔蒙调节还没有完全理解.
研究的目的:
- 确定激素信号调节FOXO脱乙化的机制.
- 阐明一个荷尔蒙依赖模块在能量平衡中的作用.
主要方法:
- 使用Drosophila melanogaster作为一个模型生物.
- 研究了Ser/Thr激酶SIK3和IIa类脱乙酶HDAC4.4的作用.
- 分析了FOXO活动,酸化和亚细胞局部化.
- 评估了的饥饿敏感性和脂质积累.
主要成果:
- 确定了SIK3和HDAC4作为调节FOXO活动的荷尔蒙依赖模块.
- 在养 (胰岛素刺激) 期间,SIK3在细胞质中化和隔离HDAC4.
- 禁食期间SIK3的失活导致HDAC4的核转位和FOXO脱.
- 由于依赖FOXO的脂解,SIK3突变表现出饥饿敏感性.
- 减少HDAC4表达恢复了SIK3突变中的脂质积累.
结论:
- 涉及SIK3和HDAC4的新型荷尔蒙调节通路控制FOXO活动和能量平衡.
- 这条通路与SIRT1通路并行运行.
- 这些发现提供了关于禁食期间代谢适应的见解.
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