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Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

  • Duteil, Delphine Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Tosic, Milica Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Lausecker, Franziska Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Nenseth, Hatice Z. Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Müller, Judith M. Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Urban, Sylvia Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Willmann, Dominica Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany
  • Petroll, Kerstin Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany - Center for Biological Systems Analysis, Freiburg, Germany
  • Messaddeq, Nadia IGBMC, Department of Functional Genomics and Cancer, Université de Strasbourg, Illkirch, France
  • Arrigoni, Laura Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
  • Manke, Thomas Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
  • Kornfeld, Jan-Wilhelm Max Planck Institute for Metabolism Research, Cologne, Germany
  • Brüning, Jens C. Max Planck Institute for Metabolism Research, Cologne, Germany
  • Zagoriy, Vyacheslav metaSysX GmbH, Am Mühlenberg 11, Potsdam-Golm, Germany
  • Meret, Michael metaSysX GmbH, Am Mühlenberg 11, Potsdam-Golm, Germany
  • Dengjel, Jörn Department of Biology, Université de Fribourg, Switzerland
  • Kanouni, Toufike Celgene Quanticel Research, San Diego, CA 92121, USA
  • Schüle, Roland Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Germany - BIOSS Centre of Biological Signalling Studies, Freiburg, Germany - Deutsches Konsortium für Translationale Krebsforschung (DKTK), Standort Freiburg, Germany -
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    18.10.2016
Published in:
  • Cell Reports. - 2016, vol. 17, no. 4, p. 1008–1021
Lysine-specific demethylase 1
Brown adipose tissue
Epigenetics
Lipid metabolism
White adipose tissue
Adipocyte
CoREST
Thermogenesis
Obesity
Carbohydrate metabolism
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Biologie
Language
  • English
Classification
Biological sciences
License
License undefined
Identifiers
Persistent URL
https://folia.unifr.ch/unifr/documents/305271
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