Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Lean but sated: Molecular Switch for a Healthy Metabolism discovered

29.06.2015

The protein complex mTORC1 is a central regulator of cell metabolism. In the active state, it stimulates anabolic processes and increases the production and storage of proteins and lipids.

Researchers from the German Leibniz Institute for Age Research in Jena and the Dutch Ageing Institute ERIBA in Groningen discovered a mechanism how mTORC1 regulates metabolism: It controls the expression of a specific variant of the transcriptional regulator C/EBPβ.


mTORC1 controls the expression of different variants of the gene regulator C/EBPβ. Suppression of the short variant in mice leads to a healthy metabolism, leanness and improved insulin sensitivity.

[Source: Lazare / www.pixabay.com]

Elimination of this variant in mice results in a healthy metabolism, leanness and improved insulin sensitivity. The study may provide a basis for novel strategies for the treatment of metabolic diseases such as obesity and type II diabetes.

The mTORC1 (mammalian target of rapamycin complex 1) is a central regulator of cell metabolism and its activity is regulated by nutrient availability and growth signals. If activated, it stimulates anabolic metabolism and enhanced production of proteins and lipids.

The resulting increase in biomass is a prerequisite for tissue growth. Hyper-activation of mTORC1 by overfeeding may result in obesity and is believed to promote metabolic disorders such as type II diabetes. In contrast, a calorie restricted diet decreases mTORC1 activity. This improves metabolic health and increases life span in many species up to mammals.

Many researchers have focused on mTORC1 function during the past years because of its crucial role in metabolism. However, little is known about factors that are specifically controlled by mTORC1 and that are responsible for the regulation of genes that are important for metabolic adjustments.

Now, researchers from Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI) in Jena, Germany, and European Research Institute for the Biology of Ageing (ERIBA) in Groningen, Netherlands, found a mechanism through which mTORC1 regulates metabolic processes. The research results were published in renowned journal EMBO Reports.

Switching on and off metabolic gene transcription.

“Researchers already know a lot about how mTORC1 is activated by nutrient supply. But little is known about the downstream factors that regulate metabolic genes and thereby determine the metabolic state of an organism”, Prof. Dr. Cornelis Calkhoven (ERIBA), former group leader at FLI, explains.

A main function of mTORC1 is the stimulation of mRNA translation, which is the crucial and final process in gene expression that results in production of the biologically active proteins. “We now found a factor – C/EBPβ – which is controlled by mTORC1”, Calkhoven continues. C/EBPβ is a gene regulator that controls various metabolic genes. Within cells, there exist two kinds of C/EBPβ: the long variant is a gene activator, whereas the short variant suppresses genes.

“Our data show that mTORC1 specifically promotes the formation of the short variant of C/EBPβ”, Dr. Christine Müller (ERIBA), former researcher at FLI, states. The researchers used a mouse model in which a mutation in the C/EBPβ gene prevents the production of the short C/EBPβ variant even if mTORC1 is activated. “Intriguingly, our data show that mice with this mutation display an improved metabolic phenotype, including reduced fat metabolism and fat accumulation, and improved insulin sensitivity and glucose tolerance”, Dr. Laura Zidek, Postdoc at FLI, emphasizes the findings.

Healthy metabolism

“The healthy metabolic phenotype we observed in our mouse model is similar to what is found under calorie restriction”, Calkhoven explains. Interestingly, these positive effects can be achieved without reduction in food intake: the mice are lean but sated.

“Our study shows that the mechanism regulating the formation of C/EBPβ variants is an important molecular switch in the metabolic pathway controlled by mTORC1. Thus, pharmacological targeting of C/EBPβ isoform expression may provide a promising strategy for the treatment of metabolic diseases such as obesity and type II diabetes thereby extending health span.

Publication
Zidek LM, Ackermann T, Hartleben G, Eichwald S, Kortman G, Kiehntopf M, Leutz A, Sonenberg N, Wang ZQ, von Maltzahn J, Müller C, Calkhoven CF. Deficiency in mTORC1-controlled 1 C/EBPβ -mRNA translation improves metabolic health in mice. EMBO Rep. 2015. pii: e201439837. DOI 10.15252/embr.201439837.

Contact
Dr. Evelyn Kästner
Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI)
Beutenbergstr. 11, 07745 Jena, Germany
Phone: +49 (0)3641-656373, Fax: +49 (0)3641-656351, E-Mail: presse@fli-leibniz.de


Background information

The Leibniz Institute for Age Research – Fritz Lipmann Institute (FLI) is the first German research organization dedicated to biomedical aging research since 2004. More than 330 members from over 30 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. For more information, please visit http://www.fli-leibniz.de.

Dutch European Research Institute for the Biology of Ageing (ERIBA) was founded by the University Medical Center Groningen (UMCG) in 2013. ERIBA is an internationally orientated research institute focusing on fundamental biological problems related to aging and age-associated diseases. See http://www.umcg.nl/EN/Research/ERIBA for more information.

The Leibniz Association connects 89 independent research institutions that range in focus from the natural, engineering and environmental sciences via economics, spatial and social sciences to the humanities. Leibniz Institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz Institutes collaborate intensively with universities – in the form of “WissenschaftsCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad. They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the institutes’ importance for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 18,100 individuals, including 9,200 researchers. The entire budget of all the institutes is approximately 1.64 billion EUR. See http://www.leibniz-association.eu for more information.

Weitere Informationen:

http://www.fli-leibniz.de - Website Leibniz Institute for Age Research - Fritz Lipmann Institute (FLI) Jena

Dr. Kerstin Wagner | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>