FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure.
FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure.
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DOI：
10.1038/ncomms1755
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发表时间：
2012-03-27
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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营养状态等环境因素可能作用于表观基因组，从而促进细胞和生物体的代谢适应。赖氨酸特异性脱甲基酶-1（LSD 1）是一种独特的核蛋白，利用黄素腺苷二核苷酸（FAD）作为辅因子。在这里，我们表明，LSD 1表观遗传调节脂肪细胞中的能量消耗基因取决于细胞FAD的可用性。我们发现，LSD 1功能的丧失，无论是通过短干扰RNA还是通过脂肪细胞中的选择性抑制剂，都会诱导许多能量消耗和线粒体代谢的调节因子，如PPARγ共激活因子-1 α，从而激活线粒体呼吸。与正常饮食小鼠的组织相比，在高脂肪饮食小鼠的脂肪组织中，LSD 1靶基因的表达减少，这可以通过抑制LSD 1功能来逆转。我们的数据表明LSD 1通过与细胞FAD生物合成偶联来调节细胞能量平衡的新机制。 赖氨酸特异性脱甲基酶1（LSD 1）从组蛋白H3的单甲基化和二甲基化赖氨酸4去除甲基并抑制转录。在这项研究中，LSD 1在体外和高脂饮食喂养的小鼠中报道了脂肪细胞能量消耗相关基因的调节作用。
Environmental factors such as nutritional state may act on the epigenome that consequently contributes to the metabolic adaptation of cells and the organisms. The lysine-specific demethylase-1 (LSD1) is a unique nuclear protein that utilizes flavin adenosine dinucleotide (FAD) as a cofactor. Here we show that LSD1 epigenetically regulates energy-expenditure genes in adipocytes depending on the cellular FAD availability. We find that the loss of LSD1 function, either by short interfering RNA or by selective inhibitors in adipocytes, induces a number of regulators of energy expenditure and mitochondrial metabolism such as PPARγ coactivator-1α resulting in the activation of mitochondrial respiration. In the adipose tissues from mice on a high-fat diet, expression of LSD1-target genes is reduced, compared with that in tissues from mice on a normal diet, which can be reverted by suppressing LSD1 function. Our data suggest a novel mechanism where LSD1 regulates cellular energy balance through coupling with cellular FAD biosynthesis. Lysine-specific demethylase 1 (LSD1) removes methyl groups from mono-methylated and dimethylated lysine 4 of histone H3 and represses transcription. In this study, a role for LSD1 in the regulation of genes involved in energy expenditure in adipocytes is reported in vitro and in mice fed on a high-fat diet.
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影响因子：
3.9
作者：
Kubo, A;Itoh, S;Kamataki, T
通讯作者：
Kamataki, T
影响因子：
4.8
作者：
Bafunno, V;Giancaspero, TA;Barile, M
通讯作者：
Barile, M
影响因子：
64.8
作者：
Felsenfeld, G;Groudine, M
通讯作者：
Groudine, M
影响因子：
11.8
作者：
Fulco, Marcella;Cen, Yana;Sartorelli, Vittorio
通讯作者：
Sartorelli, Vittorio
DOI：
10.1042/bj20090934
发表时间：
2009-10-23
期刊：
The Biochemical journal
影响因子：
--
作者：
Hill BG;Dranka BP;Zou L;Chatham JC;Darley-Usmar VM
通讯作者：
Darley-Usmar VM