title: LSD1 promotes oxidative metabolism of white adipose tissue.
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.
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Delphine
authors.initials: D
authors.lastname: Duteil
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Metzger
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Dominica
authors.initials: D
authors.lastname: Willmann
authors.affiliation: Biomedical Sciences Research Center 'Alexander Fleming', 34 Alexander Fleming Street, Vari, Athens 16672, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Karagianni
authors.affiliation: 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.
authors.forename: Nicolaus
authors.initials: N
authors.lastname: Friedrichs
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Greschik
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Günther
authors.affiliation: Universitätsklinikum Köln, Institut für Pathologie, Kerpener Strasse 62, 50937 Köln, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Buettner
authors.affiliation: Biomedical Sciences Research Center 'Alexander Fleming', 34 Alexander Fleming Street, Vari, Athens 16672, Greece.
authors.forename: Iannis
authors.initials: I
authors.lastname: Talianidis
authors.affiliation: IGBMC, Department of Functional Genomics and Cancer, Inserm U964, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.affiliation: 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.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D003080:Cold Temperature; D059305:Diet, High-Fat; D004734:Energy Metabolism; D056466:Histone Demethylases / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D051266:Nuclear Respiratory Factor 1 / Q000378:metabolism*; D010085:Oxidative Phosphorylation; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C495634:Nrf1 protein, mouse; D051266:Nuclear Respiratory Factor 1; D022702:Receptors, Adrenergic, beta-3; D056466:Histone Demethylases; C495195:KDM1A protein, human