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

Shinjiro Hino, Akihisa Sakamoto, Katsuya Nagaoka, Kotaro Anan, Yuqing Wang, Shinya Mimasu, Takashi Umehara, Shigeyuki Yokoyama, Ken Ichiro Kosai, Mitsuyoshi Nakao

Research output: Contribution to journalArticlepeer-review

173 Citations (Scopus)


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.

Original languageEnglish
Article number758
JournalNature communications
Publication statusPublished - 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy


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