Featured Research

from universities, journals, and other organizations

System in brain -- target of class of diabetes drugs -- linked to weight gain

Date:
May 2, 2011
Source:
University of Cincinnati Academic Health Center
Summary:
Researchers have determined why a certain class of diabetes drugs leads to weight gain and have found that the molecular system involved (PPAR-gamma found in the brain) is also triggered by consumption of high-fat foods. The study could lead to the modification of existing diabetes therapies and even dietary recommendations to limit the action of this nuclear receptor in the brain.

University of Cincinnati (UC) researchers have determined why a certain class of diabetes drugs leads to weight gain and have found that the molecular system involved (PPAR-γ found in the brain) is also triggered by consumption of high-fat foods.

The study could lead to the modification of existing diabetes therapies and even dietary recommendations to limit the action of this nuclear receptor in the brain.

The research, led by Randy Seeley, PhD, UC professor and Donald C. Harrison Endowed Chair in Medicine, appears as an advanced online publication May 1, 2011, in the journal Nature Medicine.

PPAR-γ is found in white adipose (fat) tissue where it regulates the production of fat cells. This new research describes an important role for PPAR-γ in the brain.

PPAR-γ is the target of a class of diabetes drugs called TZDs (thiazolidinediones). This class of drugs reduces blood glucose levels but also causes considerable weight gain. That weight gain, Seeley says, makes many patients reluctant to use these therapies particularly since many are already trying to lose weight to improve their diabetes.

Seeley and his team set out to determine whether or not the brain's PPAR-γ system was responsible for the weight gain associated with TZDs. The team also wanted to learn if this system in the brain was activated by a high-fat diet.

To do so, they used animal models to test how the class of drugs interacted with the brain PPAR-γ system. They found that by giving TZD drugs in the same manner that people take them, rats gained weight. This was because the drugs activated PPAR-γ in the brain. Thus, weight gain associated with this class of drugs may not be a result of action of PPAR-γ in fat as had been previously thought, but rather a result of a change in activity in parts of the brain known to regulate appetite.

Seeley's team went on to also show that high-fat diets result in activation of the brain PPAR-γ system. Experiments in which the activity of the brain PPAR-γ system was limited resulted in less weight gain when animals were exposed to a high-fat diet similar to diets of many Americans.

"If you artificially turn on PPAR-γ, you can increase food intake in rats," says Seeley. "If you block these receptors in animals on high-fat diets that make animals obese, animals gain less weight."

In the past, says Seeley, people thought that the production of more fat cells in response to TZD drugs was the cause of the resulting weight gain, but he adds, "Just having more fat cells is not enough to make animals or people fatter. Rather you have to eat more calories than you burn and that is exactly what happens when you turn on the brain PPAR-γ system.

"This work helps us understand the complex relationship between our fat, our appetites and type 2 diabetes."

Fat cells are actually quite protective and act as safe repositories for excess nutrients that cause damage when stored in other tissues like the liver and muscle, says Seeley. "It's when nutrients are stored in these cells that individuals are at increased risk for metabolic diseases such as type 2 diabetes."

This, he says, is why TZDs are effective at lowering glucose. The extra fat cells produced become the storage containers for nutrients that would otherwise be harmful if they are stored in other areas of the body.

"You can think of your fat tissue like a bathtub," Seeley says. "A bathtub is designed to hold water. It's a good place to store it. If you turned on the faucet but didn't have a bathtub, the water would go to other parts of your house and cause water damage."

The same is true for nutrients, says Seeley. "It is better to store them in your fat tissue "bathtub" than to have them go to other parts of your body where they can do more harm."

Seeley says PPAR-γ is a system designed at all levels to help you prepare to eat more and gain weight opening up the possibility that food we eat that can activate PPAR-γ might contribute to increasing rates of obesity.

"It tells your brain to eat more and it tells your fat tissue to add new fat cells to serve as repositories to store those extra calories."

He says the next steps would be to find ways to redesign TZDs so that they retain their important glucose-lowering function but with less access to the brain, thereby limiting weight gain.

In the longer term, Seeley says, it's important to better understand the interaction between the brain's PPAR-γ system and the specific micronutrients we consume from fat, protein and sugar.

"We know that one way to activate PPAR-γ is by exposing cells to fatty acids. If we know which ones activate PPAR-γ, we could find ways to alter diets so as to limit their ability to turn on this system that drives increased food intake, making it easier for people to avoid weight gain."

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Co-authors, all from the University of Cincinnati, include Bernadette Grayson, Bailing Li, Emily Matter, Karen Ryan and Stephen Woods.


Story Source:

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


Journal Reference:

  1. Karen K Ryan, Bailing Li, Bernadette E Grayson, Emily K Matter, Stephen C Woods, Randy J Seeley. A role for central nervous system PPAR-γ in the regulation of energy balance. Nature Medicine, 2011; DOI: 10.1038/nm.2349

Cite This Page:

University of Cincinnati Academic Health Center. "System in brain -- target of class of diabetes drugs -- linked to weight gain." ScienceDaily. ScienceDaily, 2 May 2011. <www.sciencedaily.com/releases/2011/05/110501183815.htm>.
University of Cincinnati Academic Health Center. (2011, May 2). System in brain -- target of class of diabetes drugs -- linked to weight gain. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2011/05/110501183815.htm
University of Cincinnati Academic Health Center. "System in brain -- target of class of diabetes drugs -- linked to weight gain." ScienceDaily. www.sciencedaily.com/releases/2011/05/110501183815.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
Beijing Marathon Runners Brave Hazardous Air Pollution

Beijing Marathon Runners Brave Hazardous Air Pollution

AFP (Oct. 19, 2014) Tens of thousands of runners battled thick smog at the Beijing Marathon on Sunday, with some donning masks as the levels of PM2.5 small pollutant particles soared to 16 times the maximum recommended level. Duration: 00:54 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