title: Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue.
abstract: Previous work indicated that lysine-specific demethylase 1 (Lsd1) can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT) and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT)-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.
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: Milica
authors.initials: M
authors.lastname: Tosic
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Lausecker
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Hatice Z
authors.initials: HZ
authors.lastname: Nenseth
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Müller
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Urban
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: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany; Center for Biological Systems Analysis, 79106 Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Petroll
authors.affiliation: IGBMC, Department of Functional Genomics and Cancer, Inserm U964, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Messaddeq
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, Freiburg 79108, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Arrigoni
authors.affiliation: Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, Freiburg 79108, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Manke
authors.affiliation: Max Planck Institute for Metabolism Research, 50931 Cologne, Germany.
authors.forename: Jan-Wilhelm
authors.initials: JW
authors.lastname: Kornfeld
authors.affiliation: Max Planck Institute for Metabolism Research, 50931 Cologne, Germany.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Brüning
authors.affiliation: metaSysX GmbH, Am Mühlenberg 11, 14476 Potsdam-Golm, Germany.
authors.forename: Vyacheslav
authors.initials: V
authors.lastname: Zagoriy
authors.affiliation: metaSysX GmbH, Am Mühlenberg 11, 14476 Potsdam-Golm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meret
authors.affiliation: Department of Biology, Université de Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
authors.forename: Jörn
authors.initials: J
authors.lastname: Dengjel
authors.affiliation: Celgene Quanticel Research, 9393 Towne Centre Dr., Suite 110, San Diego, CA 92121, USA.
authors.forename: Toufike
authors.initials: T
authors.lastname: Kanouni
authors.affiliation: Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany; BIOSS Centre of Biological Signalling Studies, Albert Ludwigs University, 79106 Freiburg, Germany; Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort Freiburg, 79108 Freiburg, Germany. Electronic address: roland.schuele@uniklinik-freiburg.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüle
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000235:genetics; D056466:Histone Demethylases / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D018345:Mice, Knockout; D008954:Models, Biological; D010084:Oxidation-Reduction; D015430:Weight Gain
chemical_list: D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D005947:Glucose
keywords: CoREST; adipocyte; brown adipose tissue; carbohydrate metabolism; epigenetics; lipid metabolism; lysine-specific demethylase 1; obesity; thermogenesis; white adipose tissue