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.
Original language | English |
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Pages (from-to) | 1008-1021 |
Number of pages | 14 |
Journal | Cell Reports |
Volume | 17 |
Issue number | 4 |
DOIs | |
Publication status | Published - 18 Oct 2016 |
Externally published | Yes |
Bibliographical note
Copyright the Author(s) 2016. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.Keywords
- adipocyte
- brown adipose tissue
- carbohydrate metabolism
- CoREST
- epigenetics
- lipid metabolism
- lysine-specific demethylase 1
- obesity
- thermogenesis
- white adipose tissue