Navigation Links
Researchers reveal how a single gene mutation leads to uncontrolled obesity
Date:3/18/2012

Washington, D.C. -- Researchers at Georgetown University Medical Center have revealed how a mutation in a single gene is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the right place in the brain. What results is obesity caused by a voracious appetite.

Their study, published March 18th on Nature Medicine's website, suggests there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.

The research team specifically found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain. In humans, these hormones, which are released in the body after a person eats, are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues.

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," says the study's senior investigator, Baoji Xu, Ph.D., an associate professor of pharmacology and physiology at Georgetown.

"This discovery may open up novel strategies to help the brain control body weight," he says.

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons.

For example, he has shown that during development, BDNF is important to the formation and maturation of synapses, the structures that permit neurons to send chemical signals between them. The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice.

Xu also found that the mice with the same Bdnf mutation grew to be severely obese.

Other researchers began to look at the Bdnf gene in humans, and large-scale genome-wide association studies showed Bdnf gene variants are, in fact, linked to obesity.

But, until this study, no one has been able to describe exactly how BDNF controls body weight.

Xu's data shows that both leptin and insulin stimulate synthesis of BDNF in neuronal dendrites in order to move their chemical message from one neuron to another through synapses. The intent is to keep the leptin and insulin chemical signals moving along the neuronal highway to the correct brain locations, where the hormones will turn on a program that suppresses appetite.

"If there is a problem with the Bdnf gene, neurons can't talk to each other, and the leptin and insulin signals are ineffective, and appetite is not modified," Xu says.

Now that scientists know that BDNF regulates the movement of leptin and insulin signals through brain neurons, the question is whether a faulty transmission line can be repaired.

One possible strategy would be to produce additional long-form Bdnf transcript using adeno-associated virus-based gene therapy, Xu says. But although this kind of gene therapy has proven to be safe, it is difficult to deliver across the brain blood barrier, he adds.

"The better approach might be to find a drug that can stimulate Bdnf expression in the hypothalamus," Xu says. "We have opened the door to both new avenues in basic research and clinical therapies, which is very exciting."
'/>"/>

Contact: Karen Mallet
km463@georgetown.edu
Georgetown University Medical Center
Source:Eurekalert

Related biology news :

1. NC State researchers get to root of parasite genome
2. Researchers find animal with ability to survive climate change
3. Researchers find an essential gene for forming ears of corn
4. Researchers note differences between people and animals on calorie restriction
5. Researchers study acoustic communication in deep-sea fish
6. Researchers discover that growing up too fast may mean dying young in honey bees
7. Researchers study how pistachios may improve heart health
8. UI researchers find potentially toxic substance present in Chicago air
9. Researchers develop new self-training gene prediction program for fungi
10. Case Western Reserve University researchers track Chernobyl fallout
11. Childrens National researchers develop novel anti-tumor vaccine
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/31/2016)... 2016  Genomics firm Nabsys has completed a financial ... Bready , M.D., who returned to the company in ... leadership team, including Chief Technology Officer, John Oliver ... Nurnberg and Vice President of Software and Informatics, ... Dr. Bready served as CEO of Nabsys from ...
(Date:3/21/2016)... -- Unique technology combines v ...   Xura, Inc. (NASDAQ: ... communications services, today announced it is working alongside SpeechPro ... particularly those in the Financial Services Sector, the ability ... a mobile app, alongside, and in combination with, traditional ...
(Date:3/14/2016)... NXTD ) ("NXT-ID" or the "Company"), ... the airing of a new series of commercials on Time ... 21 st .  The commercials will air on Bloomberg TV, ... the Street show. --> NXTD ) ("NXT-ID" or ... market, announces the airing of a new series of commercials ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... UTAH. (PRWEB) , ... May 25, 2016 , ... WEDI, ... healthcare information exchange, today announced that Charles W. Stellar has been named by the ... interim CEO since January 2016. As an executive leader with more than 35 years ...
(Date:5/24/2016)... La Jolla, CA (PRWEB) , ... May 24, 2016 , ... ... and financial planning for corporate executives and entrepreneurs, held The Future of San Diego ... leaders in the San Diego life science community attended the event with speakers Dr. ...
(Date:5/23/2016)... England , May 23, 2016 ... May 25 th at 10:15 a.m. ET before the ... the role genetically engineered mosquitos can play in controlling the ... carrier of the Zika virus.      (Logo: ... engineered male mosquito with a self-limiting gene. Trials in ...
(Date:5/20/2016)... ... May 20, 2016 , ... The leading Regenerative Veterinary ... most experienced veterinary clients have treated over 100 of their own patients with the ... provide the highest level of care for their patients. , The veterinarians are ...
Breaking Biology Technology: