The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.

The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism.
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DOI:
10.1038/nm.2347
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发表时间:
2011-06-12
期刊:
影响因子:
82.9
通讯作者:
--
中科院分区:
医学1区
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--
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在这里,我们报告说,转录因子CREB-H是维持正常的血浆甘油三酯(TG)水平所必需的。CREB-H缺陷型小鼠表现出继发于脂蛋白脂酶(Lpl)催化的TG清除效率低下的高脂血症(HTG),部分原因是Lpl共激活因子Apoc 2、Apoa 4和Apoa 5的表达缺陷以及Lpl抑制剂Apoc 3的同时增强。在极端HTG患者中发现了CREB 3L 3的多个非同义突变,这些突变产生了亚型或无功能的CREB-H蛋白,这表明CREB-H在人类TG代谢中起着关键作用。
Here we report that the transcription factor CREB-H is required for the maintenance of normal plasma triglyceride (TG) levels. CREB-H deficient mice displayed hypertriglyceridemia (HTG) secondary to inefficient TG clearance catalyzed by lipoprotein lipase (Lpl), partly due to defective expression of the Lpl coactivators, Apoc2, Apoa4, and Apoa5 and concurrent augmentation of the Lpl inhibitor, Apoc3. Multiple nonsynonymous mutations in CREB3L3 that produced hypomorphic or nonfunctional CREB-H protein were identified in patients with extreme HTG, implicating a critical role for CREB-H in human TG metabolism.
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