The epigenetic enzyme Lsd1 plays an important role in maintaining brown fat tissue
In mammals, three types of adipose tissues exist. White adipocytes are mainly located in the abdominal and subcutaneous areas of the body and highly adapted to store excess energy. Conversely, beige and brown adipocytes are highly energy-expending by generating heat. A team with the Freiburg researchers Prof. Dr. Roland Schuele and Dr. Delphine Duteil has now shown that the epigenetic enzyme lysine-specific demethylase 1 (Lsd1) plays a key role in maintaining the metabolic properties of brown fat.
“The changes induced by Lsd1 ablation have secondary effects on body weight gain and glucose tolerance with aging,” explains Prof. Schuele. The researchers selectively ablated Lsd1 and inactivated its catalytic activity in brown adipocytes, which triggered a profound whitening of brown adipose tissue: The colour of the brown fat cells became paler, their size increased and they started to store energy instead of expending it. By understanding these processes, scientists want to develop new strategies to counteract obesity and diabetes.
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.
Roland Schuele and Delphine Duteil are from the Department of Urology and the Clinical Research Center at the Medical Center – University of Freiburg. Schuele is a member of the Cluster of Excellence BIOSS Centre for Biological Signalling Studies at the University of Freiburg.
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 (2016). Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue. Cell Rep. 18;17(4):1008-1021. doi: 10.1016/j.celrep.2016.09.053.
Article about Roland Schuele’s research in “uni’wissen”:
Prof. Dr. Roland Schuele
Department of Urology and Clinical Research Center
Medical Center – University of Freiburg
BIOSS Centre for Biological Signalling Studies
University of Freiburg
Phone: +49 (0)761/270-63100
Rudolf-Werner Dreier | Albert-Ludwigs-Universität Freiburg im Breisgau
Flavins keep a handy helper in their pocket
25.04.2018 | University of Freiburg
Complete skin regeneration system of fish unraveled
24.04.2018 | Tokyo Institute of Technology
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
25.04.2018 | Physics and Astronomy
25.04.2018 | Physics and Astronomy
25.04.2018 | Information Technology