Featured Research

from universities, journals, and other organizations

Clue To Safer Obesity Drugs: Mechanism Links Serotonin With Regulation Of Food Intake

Date:
December 7, 2008
Source:
UT Southwestern Medical Center
Summary:
Once hailed as a miracle weight-loss drug, Fen-phen was removed from the market more than a decade ago for inducing life-threatening side effects, including heart valve lesions. Scientists are trying to understand how Fen-phen behaves in the brain in order to develop safer anti-obesity drugs with fewer side effects.

Dr. Joel Elmquist (left), professor of internal medicine and pharmacology at UT Southwestern and senior author of the study, and Dr. Yong Xu, a postdoctoral research fellows in internal medicine.
Credit: Image courtesy of UT Southwestern Medical Center

Once hailed as a miracle weight-loss drug, Fen-phen was removed from the market more than a decade ago for inducing life-threatening side effects, including heart valve lesions. Scientists at UT Southwestern Medical Center are trying to understand how Fen-phen behaves in the brain in order to develop safer anti-obesity drugs with fewer side effects.

Related Articles


In a study appearing in the Nov. 25 issue of Neuron, the researchers define a circuit in the brain that explains the ways fenfluramine, a component of Fen-phen, suppresses appetite.

"Our findings provide evidence that the neural circuit we've proposed is sufficient for the neurotransmitter serotonin to regulate food intake and body weight, " said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study. "Fen-phen works directly on this pathway. Unfortunately, that drug also adversely affects peripheral tissue such as the heart."

For the current study, the researchers engineered mice in which the expression of a serotonin receptor called 5-hydroxytryptamine 2C was blocked throughout the entire body. This was previously known to produce obese mice resistant to the anorexic actions of fenfluramine. When activated by serotonin, however, this receptor is also known to suppress appetite. Using this mouse model, the authors engineered another set of mice in which the same serotonin receptor was blocked everywhere in the body except within a group of brain cells called pro-opiomelanocortin, or POMC, neurons. The POMC neurons, which are found in the hypothalamus, are also known to play an important role in suppressing appetite and inducing weight loss.

The researchers found that the animals with no serotonin 2c receptors expectedly developed obesity as well as other metabolism disorders such as increased food intake, hyperactivity and leptin insensitivity. They also were prone to spontaneous seizures, said Dr. Elmquist.

In contrast, the mice in which the serotonin receptor was re-expressed and functioning only in the POMC neurons stayed slim and responded to fenfluramine.

"The POMC-specific reactivation of the receptor only in POMC neurons normalizes the abnormal metabolism in these mice," Dr. Elmquist said. "The animals don't eat excessively. Their hyperactivity is also gone."

Previous work from the UT Southwestern group led to the hypothesis that Fen-phen worked by activating the serotonin 2c receptor in the POMC neurons in the hypothalamus. The current work provides genetic proof supporting this model.

"Conventional wisdom is that fenfluramine increases serotonin release that then activates serotonin receptors in the brain to regulate food intake and body weight, but unfortunately, this drug also causes lesions in heart valves," he said. "If you could develop a drug that would travel to both the brain and the peripheral tissues, and then give a blocker to protect the heart, it's possible that you could prevent the harmful side effects and still aid weight loss. Admittedly, that's a bit farfetched, but this mouse model could be used to test that theory."

The team's next step is to determine whether they've identified the sole circuit required to suppress appetite and induce weight loss.

Other UT Southwestern scientists involved in the research were Drs. Yong Xu, Daisuke Kohno and Kevin Williams, postdoctoral research fellows in internal medicine; Charlotte Lee, senior research scientist; Michelle Choi, research assistant in internal medicine; Jason Anderson, student research assistant; and Dr. Jeffrey Zigman, assistant professor of internal medicine. Researchers from the University of Cambridge and Harvard Medical School also contributed.

The work was funded by the National Institutes of Health, Canadian Institute of Health, American Diabetes Association, Smith Family Foundation and Wellcome Trust.


Story Source:

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


Cite This Page:

UT Southwestern Medical Center. "Clue To Safer Obesity Drugs: Mechanism Links Serotonin With Regulation Of Food Intake." ScienceDaily. ScienceDaily, 7 December 2008. <www.sciencedaily.com/releases/2008/11/081125121238.htm>.
UT Southwestern Medical Center. (2008, December 7). Clue To Safer Obesity Drugs: Mechanism Links Serotonin With Regulation Of Food Intake. ScienceDaily. Retrieved November 26, 2014 from www.sciencedaily.com/releases/2008/11/081125121238.htm
UT Southwestern Medical Center. "Clue To Safer Obesity Drugs: Mechanism Links Serotonin With Regulation Of Food Intake." ScienceDaily. www.sciencedaily.com/releases/2008/11/081125121238.htm (accessed November 26, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Wednesday, November 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com
Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) — Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) — Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) — Researchers find that as people approach new decades in their lives they make bigger life decisions. 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