Nat Commun：一种影响能量代谢的酶

《自然—通讯》3月27日在线发表了日本熊本大学研究人员的论文，该文章报道了他们的最新研究成果，他们发现细胞核中一种酶能够抑制与能量代谢相关的基因，从而使代谢变差，这一发现将有助于了解代谢综合征的发生机制及开发相关治疗方法。

熊本大学的一个研究小组在小鼠实验中发现，在肌体处于肥胖状态时，细胞核中一种被称为“LSD1”的酶能够抑制与能量代谢有关的基因的功能。基因的功能受到抑制后，向细胞内供应能量的线粒体的活跃性就降低，导致代谢变差。研究人员向长期进食高脂肪食物的肥胖小鼠投放能够影响这种酶的药物后，发现与能量代谢有关的基因功能恢复作用，小鼠难以继续变胖，肥胖状态受到了控制。

研究人员指出，特定代谢基因的功能受到影响后将导致代谢综合征等多种疾病。代谢综合征指由人体蛋白质、脂肪、碳水化合物等物质代谢紊乱引起的一系列病理状态，包括体重超重或肥胖、高血压、高血糖、高血脂等。（生物谷 bioon.com）

doi:10.1038/ncomms1755
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FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure

Kotaro Anan；Yuqing Wang；Shinya Mimasu；Takashi Umehara；Shigeyuki Yokoyama；Ken-ichiro Kosai；Mitsuyoshi Nakao

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.