Research Abstract


FAD-dependent lysine-specific demethylase-1 regulates cellular energy expenditure

2012年3月27日 Nature Communications 3 : 758 doi: 10.1038/ncomms1755


日野 信次朗1, 坂元 顕久1, 長岡 克弥1, 阿南 浩太郎1, 王 宇清2, 三桝 信哉3,4, 梅原 崇史3, 横山 茂之3,4, 小戝 健一郎2 & 中尾 光善1,5

  1. 熊本大学発生医学研究所 細胞医学分野
  2. 鹿児島大学大学院 医歯学総合研究科 先進治療科学専攻 遺伝子治療・再生医学分野
  3. 理化学研究所 生命分子システム基盤研究領域
  4. 東京大学大学院 理学系研究科
  5. 科学技術振興機構(JST)CREST
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.