Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

Duteil, Delphine; Tosic, Milica; Lausecker, Franziska; Nenseth, Hatice Z.; Müller, Judith M.; Urban, Sylvia; Willmann, Dominica; Petroll, Kerstin; Messaddeq, Nadia; Arrigoni, Laura; Manke, Thomas; Kornfeld, Jan-Wilhelm; Brüning, Jens C.; Zagoriy, Vyacheslav; Meret, Michael; Dengjel, Jörn; Kanouni, Toufike; Schüle, Roland

doi:10.1016/j.celrep.2016.09.053

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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 -

18.10.2016

Published in:

Cell Reports. - 2016, vol. 17, no. 4, p. 1008–1021

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