Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How do muscles know what time it is?

21.08.2018

How do muscle cells prepare for the particular metabolic challenges of the day? Scientists at Helmholtz Zentrum München and Ludwig-Maximilians-Universität München (LMU), members of the German Center for Diabetes Research (DZD), have investigated this question and published their results in ‘PLOS Biology’. The study has uncovered a metabolic network which is, contrary to expectations, not controlled by the brain but rather by the ‘circadian clock’ of muscle cells.

Circadian clocks are present in all cells of the body, and have a pervasive influence on all aspects of human physiology. This is because they regulate homeostasis by anticipating rhythmic changes in behavior and nutritional state, and by compartmentalizing incompatible metabolic pathways within precise temporal windows.


The ‘circadian clock’ of muscle cells (shown here is the transverse section of a muscle fiber) controls an entire metabolic network.

© Helmholtz Zentrum München

“This applies, for example, to the use of nutrients such as fats and carbohydrates,” explains Professor Henriette Uhlenhaut. She is group leader at the Institute for Diabetes and Obesity of Helmholtz Zentrum München (IDO) and the Gene Center of LMU. “If the body’s internal clock gets out of synch, however, it can have serious consequences for the body’s metabolism. For example, it is known that shift workers are particularly susceptible to metabolic diseases such as diabetes.”

In their recent work, the team led by Uhlenhaut turned their attention to the 24-hour metabolic rhythm of muscles. “We focused specifically on two proteins that act as master regulators, positive and negative arms of the circadian clock,” says Kenneth Dyar, a scientist at the IDO and lead author of the study. “These two opposing molecules bind to DNA and trigger expression of additional proteins known to regulate lipid and protein metabolism.”

Using muscle cells from mice, the scientists determined the activity of the two proteins over the course of the day and night. “We measured everything, from DNA binding to gene expression and metabolites,” says Kenneth Dyar, explaining the researchers’ comprehensive approach. Building upon previous studies, the scientists studied the synthesis and breakdown of fats and proteins over 24 hours – an approach that might also be interesting for athletes.

Uncovering a metabolic network

In collaboration with Italian and Austrian colleagues (from the Venetian Institute of Molecular Medicine and the Universities of Padua, Graz, and Trieste) the researchers identified certain processes that are switched on at night by the regulators of the internal clock: “They include, for example, fat storage, glucose metabolism and insulin sensitivity,” explains Henriette Uhlenhaut. At the same time, opposing processes such as fatty acid oxidation and protein breakdown are throttled down, according the authors. These patterns are especially pronounced in the hours before awakening and are thought to prepare the muscles for the day ahead.

In the final step, the scientists investigated possible ways to intervene in these processes. To this end, they examined mice lacking these master regulators. Without a circadian clock, the animals were leaner, with less fat and more muscle mass. “Taken together, our work has revealed an entire metabolic network at multiple levels,” Uhlenhaut explains. “Another biologically exciting finding is that, contrary to expectations, the key regulator is not centrally located in the brain, but is in fact the internal clock of the muscle cells themselves.” In the long term, the authors will investigate the mechanisms also in humans and try to find a way for therapeutic interventions. Their hope is that it might be possible to counteract insulin resistance in type 2 diabetes or to stimulate energy use to combat obesity.

Further Information

Background:
Specifically, the authors compared the genome-wide binding of the two transcription factors BMAL1 and REV-ERBα. The authors Michaël Hubert and Katrin Fischer are participants in the Helmholtz Graduate School Environmental Health program, or HELENA for short.

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en

The Institute of Diabetes and Obesity (IDO) studies the diseases of the metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies. It seeks to discover new signaling pathways in order to develop innovative therapeutic approaches for the personalized prevention and treatment of obesity, diabetes and their concomitant diseases. IDO is part of the Helmholtz Diabetes Center (HDC). http://www.helmholtz-muenchen.de/ido

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. http://www.dzd-ev.de/en/index.html

Contact for the media:
Department of Communication, Helmholtz Zentrum München - German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 2238 - E-mail: presse@helmholtz-muenchen.de

Wissenschaftliche Ansprechpartner:

Prof. Dr. Henriette Uhlenhaut, Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Diabetes and Obesity, Ingolstädter Landstr. 1, 85764 Neuherberg - Tel. +49 89 3187 2052 - E-mail: henriette.uhlenhaut@helmholtz-muenchen.de

Originalpublikation:

Dyar, K. et al. (2018): Transcriptional programming of lipid and amino acid metabolism by the skeletal muscle circadian clock. PLOS Biology, DOI: 10.1371/journal.pbio.2005886

Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Further information:
http://www.helmholtz-muenchen.de

More articles from Life Sciences:

nachricht Something old, something new in the Ocean`s Blue
14.11.2019 | Max-Planck-Institut für Marine Mikrobiologie

nachricht AI-driven single blood cell classification: New method to support physicians in leukemia diagnostics
13.11.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New opportunities in additive manufacturing presented

Fraunhofer IFAM Dresden demonstrates manufacturing of copper components

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM in Dresden has succeeded in using Selective Electron Beam Melting (SEBM) to...

Im Focus: New Pitt research finds carbon nanotubes show a love/hate relationship with water

Carbon nanotubes (CNTs) are valuable for a wide variety of applications. Made of graphene sheets rolled into tubes 10,000 times smaller than a human hair, CNTs have an exceptional strength-to-mass ratio and excellent thermal and electrical properties. These features make them ideal for a range of applications, including supercapacitors, interconnects, adhesives, particle trapping and structural color.

New research reveals even more potential for CNTs: as a coating, they can both repel and hold water in place, a useful property for applications like printing,...

Im Focus: Magnets for the second dimension

If you've ever tried to put several really strong, small cube magnets right next to each other on a magnetic board, you'll know that you just can't do it. What happens is that the magnets always arrange themselves in a column sticking out vertically from the magnetic board. Moreover, it's almost impossible to join several rows of these magnets together to form a flat surface. That's because magnets are dipolar. Equal poles repel each other, with the north pole of one magnet always attaching itself to the south pole of another and vice versa. This explains why they form a column with all the magnets aligned the same way.

Now, scientists at ETH Zurich have managed to create magnetic building blocks in the shape of cubes that - for the first time ever - can be joined together to...

Im Focus: A new quantum data classification protocol brings us nearer to a future 'quantum internet'

The algorithm represents a first step in the automated learning of quantum information networks

Quantum-based communication and computation technologies promise unprecedented applications, such as unconditionally secure communications, ultra-precise...

Im Focus: Distorted Atoms

In two experiments performed at the free-electron laser FLASH in Hamburg a cooperation led by physicists from the Heidelberg Max Planck Institute for Nuclear physics (MPIK) demonstrated strongly-driven nonlinear interaction of ultrashort extreme-ultraviolet (XUV) laser pulses with atoms and ions. The powerful excitation of an electron pair in helium was found to compete with the ultrafast decay, which temporarily may even lead to population inversion. Resonant transitions in doubly charged neon ions were shifted in energy, and observed by XUV-XUV pump-probe transient absorption spectroscopy.

An international team led by physicists from the MPIK reports on new results for efficient two-electron excitations in helium driven by strong and ultrashort...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

High entropy alloys for hot turbines and tireless metal-forming presses

05.11.2019 | Event News

Smart lasers open up new applications and are the “tool of choice” in digitalization

30.10.2019 | Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

 
Latest News

New opportunities in additive manufacturing presented

14.11.2019 | Materials Sciences

Massive photons in an artificial magnetic field

14.11.2019 | Physics and Astronomy

Fraunhofer Radio Technology becomes part of the worldwide Telecom Infra Project (TIP)

14.11.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>