IRF4是PGC-1α的一个关键的热原转录合作伙伴
Xingxing Kong1, Alexander Banks2, Tiemin Liu1
1Division of Endocrinology, Beth Israel Deaconess Medical Center and Department of Genetics, Harvard Medical School, Boston, MA 02215, USA.
Cell
|July 5, 2014
概括
干扰素调节因子4 (IRF4) 通过激活燃烧热量作为热量的基因来驱动热生成. 这一发现揭示了IRF4是调节能源消耗和打击肥胖的一个关键因素.
科学领域:
- 细胞代谢的细胞代谢.
- 分子内分泌学分子内分泌学
- 肥胖研究的研究.
背景情况:
- 棕色脂肪组织 (BAT) 将能量作为热消散,抵消肥胖.
- 发热性基因表达是由像PGC-1α这样的协活性剂调节的.
- 与协活性剂合作的特定转录因子在很大程度上仍然未知.
研究的目的:
- 为了确定参与热生成的关键转录因子.
- 阐明IRF4在调节能源支出和适应寒冷方面的作用.
主要方法:
- 在冷和cAMP刺激下,研究了脂肪细胞中的IRF4表达.
- 在UCP1表达细胞中利用IRF4的淘汰模型.
- 研究了IRF4,PGC-1α和PRDM16在调节Ucp1表达中的相互作用.
主要成果:
- IRF4由寒冷和cAMP诱导,并促进发热基因表达,能量消耗和耐寒性.
- 在UCP1(+) 细胞中IRF4的淘汰会导致热生成的减少,肥胖和不耐寒.
- IRF4直接诱导PGC-1α和PRDM16,并与PGC-1α合作驱动Ucp1的表达.
结论:
- IRF4是热生成的一个关键的转录效应因子.
- IRF4作为能量消耗和热量产生基因表达程序的中央调节器.
- IRF4对于适应寒冷和预防肥胖至关重要.
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