EHMT1通过PRDM16复合体控制棕色脂肪细胞的命运和发热
Haruya Ohno1, Kosaku Shinoda, Kana Ohyama
11] UCSF Diabetes Center, Department of Cell and Tissue Biology, University of California, San Francisco, 35 Medical Center Way, San Francisco, California 94143-0669, USA [2].
Nature
|November 8, 2013
概括
欧基色组织素-氨酸N-甲基转移酶1 (EHMT1) 作为棕色脂肪发育中的关键酶. 失去EHMT1会影响热生成,导致肥胖和胰岛素抵抗.
科学领域:
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 棕色脂肪组织 (BAT) 将能量分散为热量,提供对低温和肥胖的防御.
- 棕色脂肪细胞来源于Myf5(+) 皮质体前体,由含有蛋白质16 (PRDM16) 复合体的PR域调节.
- 控制棕色脂肪细胞血统的特定酶组件仍未确定.
研究的目的:
- 为了确定PRDM16复合物的酶成分,这决定了棕色脂肪细胞系谱的规范.
- 为了研究 euchromatic histone-lysine N-methyltransferase 1 (EHMT1) 在棕色脂肪组织 (BAT) 发育和功能中的作用.
主要方法:
- 在棕色脂肪细胞中分析EHMT1表达和功能.
- 调查EHMT1损失对棕色脂肪特征和基因表达 in vivo的影响.
- 检查脂肪特异性EHMT1删除对热生成,肥胖和胰岛素抵抗的影响.
主要成果:
- 在PRDM16复合体内,EHMT1被确定为BAT丰富的氨基甲基转移酶,对棕色脂肪细胞命运至关重要.
- 棕色脂肪细胞中EHMT1的丧失导致棕色脂肪特征的丧失,并通过H3K9me2/3脱甲基化诱导肌肉分化.
- EHMT1稳定了PRDM16,积极调节了BAT热生成程序.
结论:
- EHMT1的功能是控制棕色脂肪细胞命运的必不可少的酶开关.
- EHMT1对于维持能量恒温,BAT介导的热生成以及预防肥胖和胰岛素抵抗至关重要.
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