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, D., Tosic, M., Lausecker, F., Nenseth, H. Z., Müller, J. M., Urban, S., et al. (2016). Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue. Cell Reports, 17, 1008-1021. doi:10.1016/j.celrep.2016.09.053.

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Item Permalink: https://hdl.handle.net/11858/00-001M-0000-002C-AF3F-8 Version Permalink: https://hdl.handle.net/21.11116/0000-0008-9B28-D

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https://www.sciencedirect.com/science/article/pii/S221112471631292X?via%3Dihub (Publisher version) Open Access status unknown

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Duteil, Delphine¹, Author
Tosic, Milica¹, Author
Lausecker, Franziska¹, Author
Nenseth, Hatice Z.¹, Author
Müller, Judith M.¹, Author
Urban, Sylvia¹, Author
Willmann, Dominica¹, Author
Petroll, Kerstin¹, Author
Messaddeq, Nadia¹, Author
Arrigoni, Laura², Author
Manke, Thomas², Author
Kornfeld, Jan-Wilhelm¹, Author
Brüning, Jens C.¹, Author
Zagoriy, Vyacheslav¹, Author
Meret, Michael¹, Author
Dengjel, Jörn¹, Author
Kanouni, Toufike¹, Author
Schüle, Roland¹, Author

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1External Organizations, ou_persistent22
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640

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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.

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Language(s): eng - English

Dates: Date issued: 2016-10-18

Publication Status: Issued

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Rev. Type: Peer

Identifiers: DOI: 10.1016/j.celrep.2016.09.053

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Title: Cell Reports

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Pages: - Volume / Issue: 17 Sequence Number: - Start / End Page: 1008 - 1021 Identifier: Other: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247