Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Elimination of specific neurons outside the brain triggers obesity

03.04.2017

New genetic technique developed

A research team led by Ana Domingos, from Instituto Gulbenkian de Ciencia (IGC; Portugal), developed a new genetic technique that allows the elimination of specific neurons of the peripheral nervous system without affecting the brain.


Nerve bundles dissected from adipose tissue of mice. Stained in orange are the neurons responsible for maintaining a normal adiposity.

Credit: Roksana Pirzgalska, IGC.

Using this novel technique in mice, the researchers were able to study the function of the neurons that innervate the adipose tissue, and saw that their elimination results in mice pounding up very quickly. Published on April 3rd in Nature Communications, this technique opens new avenues for the study of many diseases related to the peripheral nervous system and to other cells outside the brain.

Interested in studying the neurobiological mechanisms underlying obesity, Domingos' laboratory had recently discovered a set of neurons that innervate the adipose tissue, and demonstrated that the direct activation of those neurons burned fat.

The team now wanted to see if mice turned fat in the absence of these same peripheral neurons. Domingos' team was looking for ways to pinpoint their neurons of interest without affecting similar neurons that also exist in the brain.

To achieve this, Domingos laboratory collaborated with the chemist Gonçalo Bernardes at Instituto de Medicina Molecular (IMM, Portugal) and Cambridge University to develop a novel technique. The research team modified a widely used molecular tool, which is based on the use of diphtheria toxin. This toxin only kills cells that contain its receptor, which mice typically do not have, unless it is artificially introduced in specific cells that scientists want to study.

The team genetically introduced the diphtheria toxin receptor in the fat-innervating neurons of mice, which would then render neurons susceptible to the deadly action of the toxin. However, the genetic engineering also placed the diphtheria toxin receptor in other neurons in the brain that the researchers did not want to ablate. "The problem is that diphtheria toxin can cross the blood-brain barrier. Therefore, we could not use this molecular tool to eliminate peripheral neurons without affecting similar neurons that also exist in the brain", explains Ana Domingos.

To face this problem, the research team decided to chemically modify the diphtheria toxin, increasing its size and therefore limits its access to the brain. "Big molecules tend not to enter the brain, so we made the toxin bigger", further explains Ana Domingos.

Ines Mahu, PhD student in Domingos' laboratory and author of this study, describes their results: "We were able to eliminate neurons from the adipose tissue of mice, without affecting the brain. When comparing mice with or without those peripheral neurons, we observed a similar eating behavior. However, mice that lacked the sympathetic neurons became fat very quickly."

"We never saw animals getting fat so fast", adds Mafalda Pereira, the lead author of this study who was a master student at IGC, and is currently a PhD student at the Max Planck Institute for Metabolism Research in Cologne, Germany.

"This new technique allowed us to verify the importance of the neurons that innervate the adipose tissue to maintain a normal adiposity. But most importantly, it overcomes possible side effects in the brain that could result from the limitations of the previous technique. We can now perform genetic ablation outside the brain, and study the function of many peripheral cells not only for obesity but for several other diseases", highlights Ana Domingos.

###

This work was conducted at Instituto Gulbenkian de Ciência, in collaboration with researchers from Instituto de Medicina Molecular (Portugal), University of Santiago de Compostela (Spain), the Rockefeller University (USA), Yale University (USA), and University of Cambridge (UK). This work was funded by the Fundação para a Ciência e a Tecnologia (FCT, Portugal), the European Molecular Biology Organization (EMBO), and the European Community's Seventh Framework Programme.

Ana Mena | EurekAlert!

More articles from Health and Medicine:

nachricht UC San Diego researchers develop sensors to detect and measure cancer's ability to spread
06.12.2018 | University of California - San Diego

nachricht New cancer immunotherapy approach turns immune cells into tiny anti-tumor drug factories
05.12.2018 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

Inaugural "Virtual World Tour" scheduled for december

28.11.2018 | Event News

 
Latest News

A new molecular player involved in T cell activation

07.12.2018 | Life Sciences

High-temperature electronics? That's hot

07.12.2018 | Materials Sciences

Supercomputers without waste heat

07.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>