LSD1 promotes oxidative metabolism of white adipose tissue

Delphine Duteil, Eric Metzger, Dominica Willmann, Panagiota Karagianni, Nicolaus Friedrichs, Holger Greschik, Thomas Günther, Reinhard Buettner, Iannis Talianidis, Daniel Metzger and Roland Schüle ()
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Delphine Duteil: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
Eric Metzger: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
Dominica Willmann: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
Panagiota Karagianni: Biomedical Sciences Research Center ‘Alexander Fleming’, 34 Alexander Fleming Street, Vari, Athens 16672, Greece
Nicolaus Friedrichs: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
Holger Greschik: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
Thomas Günther: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg
Reinhard Buettner: Universitätsklinikum Köln, Institut für Pathologie
Iannis Talianidis: Biomedical Sciences Research Center ‘Alexander Fleming’, 34 Alexander Fleming Street, Vari, Athens 16672, Greece
Daniel Metzger: IGBMC, Inserm U964, CNRS UMR7104, Université de Strasbourg
Roland Schüle: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms5093

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