Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

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

doi:10.1016/j.celrep.2016.09.053

Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

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

^*Corresponding author for this work

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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.

Original language	English
Pages (from-to)	1008-1021
Number of pages	14
Journal	Cell Reports
Volume	17
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2016.09.053
Publication status	Published - 18 Oct 2016
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

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

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10.1016/j.celrep.2016.09.053

Publisher version (open access)Final published version, 3.12 MBLicence: CC BY-NC-ND

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Duteil, D., Tosic, M., Lausecker, F., Nenseth, H. Z., Müller, J. M., Urban, S., Willmann, D., Petroll, K., Messaddeq, N., Arrigoni, L., Manke, T., Kornfeld, J. W., Brüning, J. C., Zagoriy, V., Meret, M., Dengjel, J., Kanouni, T., & Schüle, R. (2016). Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue. Cell Reports, 17(4), 1008-1021. https://doi.org/10.1016/j.celrep.2016.09.053

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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.",

keywords = "adipocyte, brown adipose tissue, carbohydrate metabolism, CoREST, epigenetics, lipid metabolism, lysine-specific demethylase 1, obesity, thermogenesis, white adipose tissue",

author = "Delphine Duteil and Milica Tosic and Franziska Lausecker and Nenseth, {Hatice Z.} and M{\"u}ller, {Judith M.} and Sylvia Urban and Dominica Willmann and Kerstin Petroll and Nadia Messaddeq and Laura Arrigoni and Thomas Manke and Kornfeld, {Jan Wilhelm} and Br{\"u}ning, {Jens C.} and Vyacheslav Zagoriy and Michael Meret and J{\"o}rn Dengjel and Toufike Kanouni and Roland Sch{\"u}le",

note = "Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher. ",

year = "2016",

month = oct,

day = "18",

doi = "10.1016/j.celrep.2016.09.053",

language = "English",

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pages = "1008--1021",

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Duteil, D, Tosic, M, Lausecker, F, Nenseth, HZ, Müller, JM, Urban, S, Willmann, D, Petroll, K, Messaddeq, N, Arrigoni, L, Manke, T, Kornfeld, JW, Brüning, JC, Zagoriy, V, Meret, M, Dengjel, J, Kanouni, T & Schüle, R 2016, 'Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue', Cell Reports, vol. 17, no. 4, pp. 1008-1021. https://doi.org/10.1016/j.celrep.2016.09.053

TY - JOUR

T1 - Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

AU - Duteil, Delphine

AU - Tosic, Milica

AU - Lausecker, Franziska

AU - Nenseth, Hatice Z.

AU - Müller, Judith M.

AU - Urban, Sylvia

AU - Willmann, Dominica

AU - Petroll, Kerstin

AU - Messaddeq, Nadia

AU - Arrigoni, Laura

AU - Manke, Thomas

AU - Kornfeld, Jan Wilhelm

AU - Brüning, Jens C.

AU - Zagoriy, Vyacheslav

AU - Meret, Michael

AU - Dengjel, Jörn

AU - Kanouni, Toufike

AU - Schüle, Roland

N1 - Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

PY - 2016/10/18

Y1 - 2016/10/18

N2 - 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.

AB - 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.

KW - adipocyte

KW - brown adipose tissue

KW - carbohydrate metabolism

KW - CoREST

KW - epigenetics

KW - lipid metabolism

KW - lysine-specific demethylase 1

KW - obesity

KW - thermogenesis

KW - white adipose tissue

UR - http://www.scopus.com/inward/record.url?scp=84994824112&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.09.053

DO - 10.1016/j.celrep.2016.09.053

M3 - Article

C2 - 27760309

AN - SCOPUS:84994824112

SN - 2211-1247

VL - 17

SP - 1008

EP - 1021

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -

Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

Abstract

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