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Cell Rep. 2016 Oct 18;17(4):1008-1021. doi: 10.1016/j.celrep.2016.09.053.

Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue.

Author information

1
Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany.
2
Urologische Klinik und Zentrale Klinische Forschung, Klinikum der Universität Freiburg, Breisacherstrasse 66, 79106 Freiburg, Germany; Center for Biological Systems Analysis, 79106 Freiburg, Germany.
3
IGBMC, Department of Functional Genomics and Cancer, Inserm U964, CNRS UMR7104, Université de Strasbourg, 67404 Illkirch, France.
4
Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, Freiburg 79108, Germany.
5
Max Planck Institute for Metabolism Research, 50931 Cologne, Germany.
6
metaSysX GmbH, Am Mühlenberg 11, 14476 Potsdam-Golm, Germany.
7
Department of Biology, Université de Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
8
Celgene Quanticel Research, 9393 Towne Centre Dr., Suite 110, San Diego, CA 92121, USA.
9
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.

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.

KEYWORDS:

CoREST; adipocyte; brown adipose tissue; carbohydrate metabolism; epigenetics; lipid metabolism; lysine-specific demethylase 1; obesity; thermogenesis; white adipose tissue

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PMID:
27760309
PMCID:
PMC5081406
DOI:
10.1016/j.celrep.2016.09.053
[Indexed for MEDLINE]
Free PMC Article

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