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Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

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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 | Bruning, Jens C. | Zagoriy, Vyacheslav | Meret, Michael | Dengjel, Jörn | Kanouni, Toufike | Schüle, Roland

Edité par CCSD ; Elsevier Inc -

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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