Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue.
Fiche publication
Date publication
octobre 2016
Journal
Cell reports
Auteurs
Membres identifiés du Cancéropôle Est :
Mme MESSADDEQ Nadia
Tous les auteurs :
Duteil D, Tosic M, Lausecker F, Nenseth HZ, Müller JM, Urban S, Willmann D, Petroll K, Messaddeq N, Arrigoni L, Manke T, Kornfeld JW, Brüning JC, Zagoriy V, Meret M, Dengjel J, Kanouni T, Schüle R
Lien Pubmed
Résumé
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.
Mots clés
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
Référence
Cell Rep. 2016 10 18;17(4):1008-1021