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 Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>