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 Brüning, Jens C. Zagoriy, Vyacheslav Meret, Michael Dengjel, Jörn Kanouni, Toufike Schüle, Roland 2016-10-18 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. application/pdf https://folia.unifr.ch/global/documents/305271 https://folia.unifr.ch/documents/305271/files/den_lat.pdf https://folia.unifr.ch/documents/305271/files/den_lat_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1016/j.celrep.2016.09.053 info:eu-repo/semantics/openAccess License undefined Cell Reports. - 2016, vol. 17, no. 4, p. 1008–1021 Lysine-specific demethylase 1 Brown adipose tissue Epigenetics Lipid metabolism White adipose tissue Adipocyte CoREST Thermogenesis Obesity Carbohydrate metabolism info:eu-repo/classification/udc/57 Lsd1 ablation triggers metabolic reprogramming of brown adipose tissue http://purl.org/coar/resource_type/c_6501