When fat cells change their colour
The epigenetic enzyme Lsd1 plays an important role in maintaining brown fat tissue
Delphine Duteil
Lsd1 influences fat cells by using a dual mechanism, as the researchers from Freiburg revealed in their study. The enzyme inhibits the expression of the genes which contain the information for white adipocytes. Simultaneously, Lsd1 promotes the expression of genes containing information for brown adipocytes. The analyses by the team have shown that these opposing functions of Lsd1 are orchestrated by distinct complexes involving the enzyme.
Furthermore, according to the researchers’ analyses, Lsd1 is necessary to regulate metabolism, for example for fatty acid oxidation. If Lsd1 is inhibited in mice, the animals’ cells take up more glucose, their capacities to convert glucose into energy increases, and they use less fatty acid, for example. Thus, the animals significantly gain weight. An accumulation of intermediates of glycolysis – the process of the breakdown of glucose – in the organism contributes to the observed whitening of brown fat tissue. However, the study has also shown that mice in which Lsd1 was ablated are protected against glucose intolerance, which is often observed in the case of type-2 diabetes. In this illness, insulin cannot sufficiently regulate the blood sugar after glucose feed. Lsd1 inhibitors have already entered clinical trials, for which the findings of the Freiburg research team could also be useful.
Original publication
D. Duteil, M. Tosic, F. Lausecker, H.Z. Nenseth, J.M. Müller, S. Urban, D. Willmann, K. Petroll, N. Messaddeq, L. Arrigoni, T. Manke, J.W. Kornfeld, J.C. Brüning, V. Zagoriy, M. Meret, J. Dengjel, T. Kanouni, R. Schüle; "Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue"; Cell Rep.; 2016, 18;17(4):1008-1021.
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Original publication
D. Duteil, M. Tosic, F. Lausecker, H.Z. Nenseth, J.M. Müller, S. Urban, D. Willmann, K. Petroll, N. Messaddeq, L. Arrigoni, T. Manke, J.W. Kornfeld, J.C. Brüning, V. Zagoriy, M. Meret, J. Dengjel, T. Kanouni, R. Schüle; "Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue"; Cell Rep.; 2016, 18;17(4):1008-1021.
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