Featured Research

from universities, journals, and other organizations

How a single gene mutation leads to uncontrolled obesity

Date:
March 18, 2012
Source:
Georgetown University Medical Center
Summary:
Researchers 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.

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.
Credit: olly / Fotolia

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.

Related Articles


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."


Story Source:

The above story is based on materials provided by Georgetown University Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Guey-Ying Liao, Juan Ji An, Kusumika Gharami, Emily G Waterhouse, Filip Vanevski, Kevin R Jones, Baoji Xu. Dendritically targeted Bdnf mRNA is essential for energy balance and response to leptin. Nature Medicine, 2012; DOI: 10.1038/nm.2687

Cite This Page:

Georgetown University Medical Center. "How a single gene mutation leads to uncontrolled obesity." ScienceDaily. ScienceDaily, 18 March 2012. <www.sciencedaily.com/releases/2012/03/120318143904.htm>.
Georgetown University Medical Center. (2012, March 18). How a single gene mutation leads to uncontrolled obesity. ScienceDaily. Retrieved March 4, 2015 from www.sciencedaily.com/releases/2012/03/120318143904.htm
Georgetown University Medical Center. "How a single gene mutation leads to uncontrolled obesity." ScienceDaily. www.sciencedaily.com/releases/2012/03/120318143904.htm (accessed March 4, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, March 4, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mom Triumphs Over Tragedy, Helps Other Families

Mom Triumphs Over Tragedy, Helps Other Families

AP (Mar. 3, 2015) After her son, Dax, died from a rare form of leukemia, Julie Locke decided to give back to the doctors at St. Jude Children&apos;s Research Hospital who tried to save his life. She raised $1.6M to help other patients and their families. (March 3) Video provided by AP
Powered by NewsLook.com
Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

Looted and Leaking, South Sudan's Oil Wells Pose Health Risk

AFP (Mar. 3, 2015) Thick black puddles and a looted, leaking ruin are all that remain of the Thar Jath oil treatment facility, once a crucial part of South Sudan&apos;s mainstay industry. Duration: 01:13 Video provided by AFP
Powered by NewsLook.com
Woman Convicted of Poisoning Son

Woman Convicted of Poisoning Son

AP (Mar. 3, 2015) A woman who blogged for years about her son&apos;s constant health woes was convicted Monday of poisoning him to death by force-feeding heavy concentrations of sodium through his stomach tube. (March 3) Video provided by AP
Powered by NewsLook.com
Treadmill Test Can Predict Chance Of Death Within A Decade

Treadmill Test Can Predict Chance Of Death Within A Decade

Newsy (Mar. 2, 2015) Johns Hopkins researchers analyzed 58,000 heart stress tests to come up with a formula that predicts a person&apos;s chances of dying in the next decade. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

    Health News

      Environment News

        Technology News



          Save/Print:
          Share:

          Free Subscriptions


          Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

          Get Social & Mobile


          Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

          Have Feedback?


          Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
          Mobile: iPhone Android Web
          Follow: Facebook Twitter Google+
          Subscribe: RSS Feeds Email Newsletters
          Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins