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Nat Commun. 2014 Jun 10;5:4093. doi: 10.1038/ncomms5093.

LSD1 promotes oxidative metabolism of white adipose tissue.

Author information

1
Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
2
Biomedical Sciences Research Center 'Alexander Fleming', 34 Alexander Fleming Street, Vari, Athens 16672, Greece.
3
1] Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany [2] Universitätsklinikum Köln, Institut für Pathologie, Kerpener Strasse 62, 50937 Köln, Germany.
4
Universitätsklinikum Köln, Institut für Pathologie, Kerpener Strasse 62, 50937 Köln, Germany.
5
IGBMC, Department of Functional Genomics and Cancer, Inserm U964, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
6
1] Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany [2] BIOSS Centre of Biological Signalling Studies, Albert-Ludwigs University, 79106 Freiburg, Germany [3] Deutsche Konsortium für Translationale Krebsforschung (DKTK), Standort, Freiburg, Germany.

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 β3-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.

PMID:
24912735
PMCID:
PMC4112219
DOI:
10.1038/ncomms5093
[Indexed for MEDLINE]
Free PMC Article

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