Featured Research

from universities, journals, and other organizations

New brain target for appetite control identified

Date:
June 7, 2012
Source:
Columbia University Medical Center
Summary:
Researchers have identified a brain receptor that appears to play a central role in regulating appetite. The findings could lead to new drugs for preventing or treating obesity.

Researchers at Columbia University Medical Center (CUMC) have identified a brain receptor that appears to play a central role in regulating appetite. The findings, published June 7 in the online edition of Cell, could lead to new drugs for preventing or treating obesity.

"We've identified a receptor that is intimately involved in regulating food intake," said study leader Domenico Accili, MD, professor of Medicine at CUMC. "What is especially encouraging is that this receptor is belongs to a class of receptors that turn out to be good targets for drug development, making it a highly 'druggable' target. In fact, several existing medications already seem to interact with this receptor. So, it's possible that we could have new drugs for obesity sooner rather than later."

In their search for new targets for obesity therapies, scientists have focused on the hypothalamus, a tiny brain structure that regulates appetite. Numerous studies suggest that the regulatory mechanism is concentrated in neurons that express a neuropeptide, or brain modulator, called AgRP. But the specific factors that influence AgRP expression are not known.

The CUMC researchers found new clues to appetite control by tracing the actions of insulin and leptin. Both hormones are involved in maintaining the body's energy balance, and both are known to inhibit AgRP. "Surprisingly, blocking either the insulin or leptin signaling pathway has little effect on appetite," says Dr. Accili. "We hypothesized that both pathways have to be blocked simultaneously in order to influence feeding behavior."

To test their hypothesis, the researchers created a strain of mice whose AgRP neurons lack a protein that is integral to both insulin and leptin signaling. As the researchers hypothesized, removing this protein -- Fox01 -- had a profound effect on the animals' appetite. "Mice that lack Fox01 ate less and were leaner than normal mice," said lead author Hongxia Ren, PhD, associate research scientist in Medicine. "In addition, the Fox01-deficient mice had better glucose balance and leptin and insulin sensitivity -- all signs of a healthier metabolism."

Since Fox01 is a poor drug target, the researchers searched for other ways to inhibit the action of this protein. Using gene-expression profiling, they found a gene that is highly expressed in mice with normal AgRP neurons but is effectively silenced in mice with Fox01-deficient neurons. That gene is Gpr17 (for G-protein coupled receptor 17), which produces a cell-surface receptor called Gpr17.

To confirm that the receptor is involved in appetite control, the researchers injected a Gpr17 activator into normal mice, and their appetite increased. Conversely, when the mice were given a Gpr17 inhibitor, their appetite decreased. Similar injections had no effect on Fox01-deficient mice.

According to Dr. Accili, there are several reasons why Gpr17, which is also found in humans, would be a good target for anti-obesity medications. Since Grp17 is part of the so-called G-protein-coupled receptor family, it is highly druggable. About a third of all existing drugs work through G-protein-coupled receptors. In addition, the receptor is abundant in AgRP neurons but not in other neurons, which should limit unwanted drug side effects.

Dr. Accili and Dr. Ren's paper is titled, "G protein-coupled purinergic receptor GPR17 mediates orexigenic effects of FoxO1 in AgRP neurons." The other contributors are Ian J. Orozco (CUMC), Ya Su (Albert Einstein College of Medicine, Bronx, NY), Shigetomo Suyama (Yale University School of Medicine), Roger Gutiérrez-Juárez (Einstein), Tamas L. Horvath (Yale), Sharon L. Wardlaw (CUMC), Leona Plum (CUMC), and Ottavio Arancio (CUMC).

The study was supported by grants from the National Institutes of Health (DK58282, DK57539, DK80003, DK45024, NS49442, and DK63608).


Story Source:

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


Journal Reference:

  1. Hongxia Ren, Ian J. Orozco, Ya Su, Shigetomo Suyama, Roger Gutiérrez-Juárez, Tamas L. Horvath, Sharon L. Wardlaw, Leona Plum, Ottavio Arancio, Domenico Accili. FoxO1 Target Gpr17 Activates AgRP Neurons to Regulate Food Intake. Cell, 2012; 149 (6): 1314 DOI: 10.1016/j.cell.2012.04.032

Cite This Page:

Columbia University Medical Center. "New brain target for appetite control identified." ScienceDaily. ScienceDaily, 7 June 2012. <www.sciencedaily.com/releases/2012/06/120607122203.htm>.
Columbia University Medical Center. (2012, June 7). New brain target for appetite control identified. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2012/06/120607122203.htm
Columbia University Medical Center. "New brain target for appetite control identified." ScienceDaily. www.sciencedaily.com/releases/2012/06/120607122203.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) — The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) — An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) — Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
CDC Calls for New Ebola Safety Guidelines

CDC Calls for New Ebola Safety Guidelines

AP (Oct. 20, 2014) — Centers for Disease Control and Prevention Director Dr. Tom Frieden laid out new guidelines for health care workers when dealing with the deadly Ebola virus including new precautions when taking off personal protective equipment. (Oct. 20) Video provided by AP
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