Featured Research

from universities, journals, and other organizations

Potential mechanisms for future anti-obesity drugs identified

Date:
March 4, 2011
Source:
University of Pennsylvania
Summary:
Scientists have identified the neurological and cellular signaling mechanisms that contribute to satiety -- the sensation of feeling full -- and the subsequent body-weight loss produced by drugs used to treat Type 2 diabetes. More comprehensive knowledge of these mechanisms could form the basis for anti-obesity medications.

An interdisciplinary group of researchers at the University of Pennsylvania has, for the first time, identified the neurological and cellular signaling mechanisms that contribute to satiety -- the sensation of feeling full -- and the subsequent body-weight loss produced by drugs used to treat type 2 diabetes. More comprehensive knowledge of these mechanisms could form the basis for anti-obesity medications.

Related Articles


The group was led by Matthew Hayes of the School of Medicine's Psychiatry Department, Harvey Grill of the Psychology Department in the School of Arts and Sciences and Kendra Bence of the School of Veterinary Medicine's Animal Biology Department. Their research was aided by a team of postdoctoral and doctoral fellows, as well as technicians and undergraduate students at Penn.

The study was published in the March 2 edition of the journal Cell Metabolism.

While no pharmaceutical treatment for obesity currently exists, type 2 diabetes drugs targeting the hormone glucagon-like-peptide-1, or GLP-1, for insulin production may hold promise. These drugs were known to promote weight loss, simply as a result of patients eating less. Researchers, however, could not explain exactly what caused this change in behavior.

Naturally occurring GLP-1 is made in primarily two distinct locations in the body, the gut and the brain. Much of the previous research in this area has focused on the former at the expense of the latter when attempting to identify the relevant population of GLP-1 receptors that may mediate the suppression in food intake by pharmaceutical GLP-1 drugs.

"Identifying both the site-of-action and mechanisms that accounts for the body weight loss of these GLP-1 drugs puts us one step closer to developing effective, FDA-approved, treatments for obesity," Hayes said.

"Ignoring the brain is not the right strategy, as these drugs are certainly engaging multiple, distributed centers in the brain governing energy balance regulation," Grill said.

The Penn group not only identified a necessary part of the brain which mediates the food intake suppression effect produced by these drugs, the nucleus tractus solitarius, or NTS, but also the cellular signaling pathways required for production of GLP-1's satiety effects.

"GLP-1's ability to alter these specific signaling pathways within the NTS of the brainstem may account for the suppression in food intake and body weight by altering the long-term neurochemistry and connectivity of this region of the brain with higher-order brain centers that also regulate energy balance," Bence said.

Many researchers have tried to determine precisely how GLP-1 and other satiating signals work, especially since in obese individuals, the brain fails to correctly perceive and respond to naturally occurring energy balance signals from the body. This faulty signaling underscores the importance of pharmacological treatments, such as the long-acting GLP-1 drugs that are effective in engaging brain signaling to reduce excessive food intake and possibly obesity.

That the Penn researchers were able to demonstrate a potential neurochemical mechanism of weight loss for a class of drugs already used in the treatment of type 2 diabetes provides a missing piece of the puzzle for future FDA-approved anti-obesity drugs.

"If we can identify other chemical signals or hormones that act on the same pathways that we've shown here, then by combined action you have a coordinated, orchestrated symphony of weight suppression," Hayes said.

This research was conducted by Hayes, Grill and Bence, along with Theresa M. Leichner, research specialist; Shiru Zhao, graduate student; Grace S. Lee and Amy Chowansky, undergraduate researchers; and Scott E. Kanoski, postdoctoral fellow, all in the Psychology Department, as well as Penn Vet's Derek Zimmer, research specialist, and Bart C. De Jonghe, postdoctoral fellow.

The research was supported by the National Institutes of Health, The Institute for Diabetes, Obesity and Metabolism at the University of Pennsylvania and The Obesity Society.


Story Source:

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


Journal Reference:

  1. Matthew R. Hayes, Theresa M. Leichner, Shiru Zhao, Grace S. Lee, Amy Chowansky, Derek Zimmer, Bart C. De Jonghe, Scott E. Kanoski, Harvey J. Grill, Kendra K. Bence. Intracellular Signals Mediating the Food Intake-Suppressive Effects of Hindbrain Glucagon-like Peptide-1 Receptor Activation. Cell Metabolism, Volume 13, Issue 3, 320-330, 2 March 2011 DOI: 10.1016/j.cmet.2011.02.001

Cite This Page:

University of Pennsylvania. "Potential mechanisms for future anti-obesity drugs identified." ScienceDaily. ScienceDaily, 4 March 2011. <www.sciencedaily.com/releases/2011/03/110303111806.htm>.
University of Pennsylvania. (2011, March 4). Potential mechanisms for future anti-obesity drugs identified. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2011/03/110303111806.htm
University of Pennsylvania. "Potential mechanisms for future anti-obesity drugs identified." ScienceDaily. www.sciencedaily.com/releases/2011/03/110303111806.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
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