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


ABSTRACT: 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 PPAR? coactivator-1? 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.

SUBMITTER: Hino S 

PROVIDER: S-EPMC3316891 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

Hino Shinjiro S   Sakamoto Akihisa A   Nagaoka Katsuya K   Anan Kotaro K   Wang Yuqing Y   Mimasu Shinya S   Umehara Takashi T   Yokoyama Shigeyuki S   Kosai Ken-Ichiro K   Nakao Mitsuyoshi M  

Nature communications 20120327


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 b  ...[more]

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