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Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue
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 oxidativ...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081406/ https://www.ncbi.nlm.nih.gov/pubmed/27760309 http://dx.doi.org/10.1016/j.celrep.2016.09.053 |
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author | 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 |
author_facet | 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 |
author_sort | Duteil, Delphine |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5081406 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-50814062016-10-28 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 Cell Rep Article 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. Cell Press 2016-10-18 /pmc/articles/PMC5081406/ /pubmed/27760309 http://dx.doi.org/10.1016/j.celrep.2016.09.053 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article 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 Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue |
title | Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue |
title_full | Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue |
title_fullStr | Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue |
title_full_unstemmed | Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue |
title_short | Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue |
title_sort | lsd1 ablation triggers metabolic reprogramming of brown adipose tissue |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081406/ https://www.ncbi.nlm.nih.gov/pubmed/27760309 http://dx.doi.org/10.1016/j.celrep.2016.09.053 |
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