Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Helmholtz Researchers Identify Genetic Switch Regulating Satiety and Body Weight

29.02.2016

A team of researchers at Helmholtz Zentrum München, Technische Universität München and the German Center for Diabetes Research (DZD) has identified a new mechanism that regulates the effect of the satiety hormone leptin. The study published in the journal ‘Nature Communications’ identified the enzyme HDAC5 as key factor in our control of body weight and food intake and potential target against the Yoyo dieting effect. Click here for a video interview with the principal investigator: https://vimeo.com/153080045

Why do we get fat and why is it so difficult for so many people to keep off excess weight? Researchers in the Reseach Unit Neurobiology of Diabetes led by Dr. Paul Pfluger and at the Institute for Diabetes and Obesity led by Prof. Dr. Matthias Tschöp have now identified a new component in the complex fine-tuning of body weight and food intake.


HDAC5 (red) is a key factor in neurons for the control of food intake, astrocytes are stained in green.

Source: Helmholtz Zentrum München

They found that the enzyme histone deacetylase 5 (HDAC5) has a significant influence on the effect of the hormone leptin*. This hormone plays a crucial role in triggering satiety and thus on how the body adapts to a changing food environment.

Pfluger describes the results as follows: ”HDAC5 is an important link in the communication between our fat tissue and hunger centers in the brain.” Initial experiments have shown that the production and activity of HDAC5 in our control center for energy balance, the hypothalamus, is increased by a high-fat diet, by enlarged fat deposits and by the satiety hormone leptin.

Dhiraj Kabra, first author of the study, added: “HDAC5 is a molecular switch in the brain that helps the body to recognize how full the fat depots are. Without HDAC5, we cannot adapt our food intake or curb our fat deposition.”

Disruption of the signaling pathway leads to obesity

According to the scientists, mice unable to produce HDAC5 respond significantly worse to leptin – a condition referred to as leptin resistance. They show a continuously increased food intake and – in comparison to mice with intact HDAC5 – show increased obesity, i.e. they get fat. Through targeted activation of HDAC5 the team was able to reverse this effect, and thereby enabling obese animals to loose fat mass and body weight.

“The restoration of leptin sensitivity is an important step on the path towards sustainable weight loss and towards combating potential sequelae of obesity such as type 2 diabetes,” said study leader Pfluger. “In addition to the essential changes in diet and exercise behavior, in the future the individual components of the leptin effect could be potential drug targets to support the weight loss process.“ One of these essential components – HDAC5 – has already been identified. “However,” Pfluger concluded, “it remains to be seen in the coming years whether this enzyme will be a suitable target for combating obesity in humans.”

Further Information

Background:
* Leptin is secreted by fat tissue in direct correlation to body fat mass, thereby signaling to neurons in the brain that the fat stores are full. This leads to a negative energy balance whereupon the body reduces food intake, which ultimately leads to a reduction of body weight and fat storage. As a consequence, in the reduced fat stores less leptin is released, food intake is increased, and the fat stores and body weight are increased.

Specifically, the researchers showed that HDAC5 deacetylates the transcription factor STAT3, whereupon STAT3 can migrate to the leptin receptor. If STAT3 is phosphorylated (activated) there, it migrates back to the cell nucleus and binds to the DNA to activate gene and behavior programs that ultimately cause the reduction of food intake. If HDAC5 is absent (such as here after genetic deletion), STAT3 accumulates as hyper-acetylated and thus inactive protein in the cell nucleus. The leptin signaling pathway is thus switched off, subsequently suppressing the feeling of satiety. This study describes for the first time a direct interaction of the two molecules.

Original publication:
Kabra, DG et al. (2015). Hypothalamic Leptin Action is Mediated by Histone Deacetylase 5, Nature Communications, DOI: 10.1038/NCOMMS10782

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München 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/index.html

Technische Universität München (TUM) is one of Europe’s leading research universities, with around 500 professors, 10,000 academic and non-academic staff, and 36,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, reinforced by schools of management and education. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel and Carl von Linde have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, it regularly places among the best universities in Germany. http://www.tum.de/en/homepage

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/en/ido/index.html

The Research Unit ‘NeuroBiology of Diabetes’ (NBD) at Helmholtz Zentrum München studies the role of the central nervous system (CNS) as potential common denominator for obesity and diabetes type 2. NBD, which is associated with the IDO and part of the HDC and DZD, aims to understand the exact molecular underpinnings for leptin resistance and weight cycling and our adaptive physiological response to changes in the environment. http://www.helmholtz-muenchen.de/nbd

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 (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 3187 2238 - Fax: +49 89 3187 3324 – E-mail: presse@helmholtz-muenchen.de

Scientific contact at Helmholtz Zentrum München:
Dr. Paul Pfluger, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute for Diabetes and Obesity, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 3187 2104 - E-mail: paul.pfluger@helmholtz-muenchen.de

Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

Further reports about: Diabetes Environmental Health Genetic HDAC5 Helmholtz diseases energy balance food intake

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

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

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>