期刊
CELL REPORTS
卷 17, 期 4, 页码 1008-1021出版社
CELL PRESS
DOI: 10.1016/j.celrep.2016.09.053
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资金
- European Research Council (ERC AdGrant) [322844]
- Deutsche Forschungsgemeinschaft [SFB 992, SFB 850, SFB 746, Schu688/12-1]
- European Research Council (ERC) [322844] Funding Source: European Research Council (ERC)
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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