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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind17
Udgave nummer4
Sider (fra-til)1008-1021
Antal sider14
ISSN2211-1247
DOI
StatusUdgivet - 18. okt. 2016

Bibliografisk note

Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Fingeraftryk Dyk ned i forskningsemnerne om 'Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue'. Sammen danner de et unikt fingeraftryk.

Citationsformater