Duteil 2016 Cell Rep
|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 Rep 17:1008-21.|
Duteil D, Tosic M, Lausecker F, Nenseth HZ, Mueller JM, Urban S, Willmann D, Petroll K, Messaddeq N, Arrigoni L, Manke T, Kornfeld JW, Bruening JC, Zagoriy V, Meret M, Dengjel J, Kanouni T, Schuele R (2016) Cell Rep
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.
Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
• Keywords: CoREST, Adipocyte, Brown adipose tissue, Carbohydrate metabolism, Epigenetics, Lipid metabolism, Lysine-specific demethylase 1, Obesity, Thermogenesis, White adipose tissue
• O2k-Network Lab: DE Freiburg Schuele R
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Mouse Tissue;cell: Fat Preparation: Permeabilized tissue
Coupling state: ET Pathway: F, N, S, NS HRR: Oxygraph-2k