Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Insulin action in the brain can lead to obesity

07.06.2011
Researchers decode an important mechanism through which insulin in the hypothalamus controls the body's energy balance

Fat-rich food makes you fat. Behind this simple equation lie complex signalling pathways, through which the neurotransmitters in the brain control the body's energy balance.


This is a visualization of how insulin affects the SF-1 neurons of the hypothalamus. After stimulation with insulin, the SF-1 cells (red) form the signaling molecule PiP3 (green). (Blue: cell nucleus) Credit: Max Planck Institute for Neurological Research

Scientists at the Cologne-based Max Planck Institute for Neurological Research and the Cluster of Excellence in Cellular Stress Responses in Ageing-associated Diseases (CECAD) at the University of Cologne have clarified an important step in this complex control circuit. They have succeeded in showing how the hormone insulin acts in the part of the brain known as the ventromedial hypothalamus.

The consumption of high-fat food causes more insulin to be released by the pancreas. This triggers a signalling cascade in special nerve cells in the brain, the SF-1 neurons, in which the enzyme P13-kinase plays an important role. Over the course of several intermediary steps, the insulin inhibits the transmission of nerve impulses in such a way that the feeling of satiety is suppressed and energy expenditure reduced. This promotes overweight and obesity.

The hypothalamus plays an important role in energy homeostasis: the regulation of the body's energy balance. Special neurons in this part of the brain, known as POMC cells, react to neurotransmitters and thus control eating behaviour and energy expenditure. The hormone insulin is an important messenger substance. Insulin causes the carbohydrate consumed in food to be transported to target cells (e.g. muscles) and is then available to these cells as an energy source. When high-fat food is consumed, more insulin is produced in the pancreas, and its concentration in the brain also increases. The interaction between the insulin and the target cells in the brain also plays a crucial role in the control of the body's energy balance. However, the precise molecular mechanisms that lie behind the control exercised by insulin remain largely unclear.

A research group led by Jens Brüning, Director of the Max Planck Institute for Neurological Research and scientific coordinator of the CECAD (Cellular Stress Responses in Aging-Associated Diseases) cluster of excellence at the University of Cologne has achieved an important step in the explanation of this complex regulatory process. As the scientists have shown, insulin in the SF-1 neurons – another group of neurons in the hypothalamus – triggers a signalling cascade. Interestingly, however, these cells appear only to be regulated by insulin when high-fat food is consumed and in the case of overweight. The enzyme P13-kinase plays a central role in this cascade of messenger substances. In the course of the intermediary steps in the process, the enzyme activates ion channels and thereby prevents the transmission of nerve impulses. The researchers suspect that the SF-1 cells communicate in this way with the POMC cells.

Kinases are enzymes that activate other molecules through phosphorylation – the addition of a phosphate group to a protein or other organic molecule. "If insulin binds to its receptor on the surface of the SF-1 cells, it triggers the activation of the PI3-kinase," explains Tim Klöckener, first author of the study. "The PI3-kinase, in turn, controls the formation of PIP3, another signalling molecule, through phosphorylation. PIP3 makes the corresponding channels in the cell wall permeable to potassium ions." Their influx causes the neuron to 'fire' more slowly and the transmission of electrical impulses is suppressed.

"Therefore, in overweight people, insulin probably indirectly inhibits the POMC neurons, which are responsible for the feeling of satiety, via the intermediary station of the SF-1 neurons," supposes the scientist. "At the same time, there is a further increase in food consumption." The direct proof that the two types of neurons communicate with each other in this way still remains to be found, however.

In order to find out how insulin acts in the brain, the Cologne-based scientists compared mice that lacked an insulin receptor on the SF-1 neurons with mice whose insulin receptors were intact. With normal food consumption, the researchers discovered no difference between the two groups. This would indicate that insulin does not exercise a key influence on the activity of these cells in slim individuals. However, when the rodents were fed high-fat food, those with the defective insulin receptor remained slim, while their counterparts with functional receptors rapidly gained weight. The weight gain was due to both an increase in appetite and reduced calorie expenditure. This effect of insulin could constitute an evolutionary adaptation by the body to an irregular food supply and extended periods of hunger: if an excess supply of high-fat food is temporarily available, the body can lay down energy reserves particularly effectively through the action of insulin.

It is not currently possible to say whether the findings of this research will eventually help to facilitate targeted intervention in the body's energy balance. "We are currently still very far away from a practical application," says Jens Brüning. "Our objective is to find out how hunger and the feeling of satiety arise. Only when we understand the entire system at work here, we will be able to start developing treatments."

Original publication:

Tim Klöckener, Simon Hess, Bengt F. Belgardt, Lars Paeger, Linda A.W. Verhagen, Andreas Husch, Jong-Woo Sohn, Brigitte Hampel, Harveen Dhillon, Jeffrey M. Zigman, Bradford B. Lowell, Kevin W. Williams, Joel K. Elmquist, Tamas L. Horvath, Peter Kloppenburg, Jens C. Brüning
High-fat Feeding Promotes Obesity via Insulin Receptor/P13k-Dependent Inhibition of SF-1 VMH Neurons

Nature Neuroscience, June 5th 2011

Professor Jens C. Brüning | EurekAlert!
Further information:
http://www.nf.mpg.de

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>