Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

Cell Rep. 2016 Oct 18;17(4):1008-1021. doi: 10.1016/j.celrep.2016.09.053.


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.

Keywords: CoREST; adipocyte; brown adipose tissue; carbohydrate metabolism; epigenetics; lipid metabolism; lysine-specific demethylase 1; obesity; thermogenesis; white adipose tissue.

MeSH terms

  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, White / metabolism
  • Animals
  • Gene Deletion*
  • Gene Expression Regulation
  • Glucose / metabolism
  • Glycolysis / genetics
  • Histone Demethylases / metabolism*
  • Lipid Metabolism / genetics
  • Mice, Knockout
  • Models, Biological
  • Oxidation-Reduction
  • Weight Gain


  • Histone Demethylases
  • KDM1a protein, mouse
  • Glucose