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 (1, 2) , Laura Arrigoni , Thomas Manke , Jan-Wilhelm Kornfeld , Jens C. Bruning , Vyacheslav Zagoriy , Michael Meret , Jörn Dengjel , Toufike Kanouni , Roland Schüle

1 IGBMC - Institut de Génétique et de Biologie Moléculaire et Cellulaire
2 IGBMC - Institut de génétique et biologie moléculaire et cellulaire

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.

Domaines: Biologie cellulaire

Delphine Duteil, Milica Tosic, Franziska Lausecker, Hatice Z. Nenseth, Judith M. Müller, et al.. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue. Cell Reports, 2016, 17 (4), pp.1008-1021. ⟨10.1016/j.celrep.2016.09.053⟩. ⟨hal-03685158⟩