[PDF][PDF] Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue

D Duteil, M Tosic, F Lausecker, HZ Nenseth, JM Müller… - Cell reports, 2016 - cell.com
D Duteil, M Tosic, F Lausecker, HZ Nenseth, JM Müller, S Urban, D Willmann, K Petroll
Cell reports, 2016cell.com
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 …
Summary
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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