LSD1 promotes oxidative metabolism of white adipose tissue.
Nat Commun
; 5: 4093, 2014 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-24912735
ABSTRACT
Exposure to environmental cues such as cold or nutritional imbalance requires white adipose tissue (WAT) to adapt its metabolism to ensure survival. Metabolic plasticity is prominently exemplified by the enhancement of mitochondrial biogenesis in WAT in response to cold exposure or ß3-adrenergic stimulation. Here we show that these stimuli increase the levels of lysine-specific demethylase 1 (LSD1) in WAT of mice and that elevated LSD1 levels induce mitochondrial activity. Genome-wide binding and transcriptome analyses demonstrate that LSD1 directly stimulates the expression of genes involved in oxidative phosphorylation (OXPHOS) in cooperation with nuclear respiratory factor 1 (Nrf1). In transgenic (Tg) mice, increased levels of LSD1 promote in a cell-autonomous manner the formation of islets of metabolically active brown-like adipocytes in WAT. Notably, Tg mice show limited weight gain when fed a high-fat diet. Taken together, our data establish LSD1 as a key regulator of OXPHOS and metabolic adaptation in WAT.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosforilação Oxidativa
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Temperatura Baixa
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Fator 1 Nuclear Respiratório
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Tecido Adiposo Branco
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Adipócitos Marrons
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Histona Desmetilases
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Mitocôndrias
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article