Featured Research

from universities, journals, and other organizations

New target for treating diabetes and obesity

Date:
August 2, 2012
Source:
Washington University School of Medicine
Summary:
Researchers have identified a potential target for treating diabetes and obesity. Studying mice, they found that when the target protein was disabled, the animals became more sensitive to insulin and were less likely to get fat.

Sections of white fat taken from normal mice (left) and from mice without an enzyme called fatty acid synthase (FAS) in their fat cells (right). Mice without FAS can eat a high-fat diet without becoming obese.
Credit: Semenkovich lab

Researchers at Washington University School of Medicine in St. Louis have identified a potential target for treating diabetes and obesity.

Studying mice, they found that when the target protein was disabled, the animals became more sensitive to insulin and were less likely to get fat even when they ate a high-fat diet that caused their littermates to become obese.

The findings are published online in the journal Cell Metabolism.

The researchers studied how the body manufactures fat from dietary sources such as carbohydrates. That process requires an enzyme called fatty acid synthase (FAS). Mice engineered so that they don't make FAS in their fat cells can eat a high-fat diet without becoming obese.

"Mice without FAS were significantly more resistant to obesity than their wild-type littermates," says first author Irfan J. Lodhi, PhD. "And it wasn't because they ate less. The mice ate just as much fatty food, but they metabolized more of the fat and released it as heat."

To understand why that happened, Lodhi, a research instructor in medicine, analyzed their fat cells. Mice have two types of fat: white fat and brown fat. White fat stores excess calories and contributes to obesity. Brown fat helps burn calories and protects against obesity.

In mice genetically blocked from making fatty acid synthase in fat cells, Lodhi and his colleagues noticed that the animals' white fat was transformed into tissue that resembled brown fat.

"These cells are 'brite' cells, brown fat found where white fat cells should be," Lodhi says. "They had the genetic signature of brown fat cells and acted like brown fat cells. Because the mice were resistant to obesity, it appears that fatty acid synthase may control a switch between white fat and brown fat. When we removed FAS from the equation, white fat transformed into brite cells that burned more energy."

Determining whether humans also have brown fat has been somewhat controversial throughout the years, but recent studies elsewhere have confirmed that people have it.

"It definitely exists, and perhaps the next strategy we'll use for treating people with diabetes and obesity will be to try to reverse their problems by activating these brown fat cells," says senior investigator Clay F. Semenkovich, MD.

Semenkovich, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research, says the new work is exciting because FAS provides a target that may be able to activate brown fat cells to treat obesity and diabetes. But even better, he says it may be possible to target a protein downstream from FAS to lower the risk for potential side effects from the therapy.

That is possible because the scientists learned that the FAS pathway involves a family of proteins known as the PPARs (peroxisome proliferator-activated receptors). PPARs are important in lipid metabolism. One of them, PPAR-alpha, helps burn fat, but the related protein, PPAR-gamma manufactures fat and helps store it.

Lodhi and Semenkovich noticed that in mice without FAS in their fat cells, activity of PPAR-alpha (the fat burner) was increased, while PPAR-gamma (the fat builder) activity decreased.

A protein called PexRAP (Peroxisomal Reductase Activating PPAR-gamma) turned out to be a downstream mediator of the effects of FAS and a key regulator of the PPAR-gamma, fat-storing pathway. When the researchers blocked PexRAP in fat cells in mice, they also interfered with the manufacture and buildup of fat.

"There was decreased fat when we blocked PexRAP," Lodhi says. "Those mice also had improved glucose metabolism, so we think that inhibiting either fatty acid synthase or PexRAP might be good strategies for treating obesity and diabetes."

Several pharmaceutical companies are working on FAS inhibitors. Meanwhile, the discovery that inhibiting PexRAP also makes the animals less obese and less diabetic has convinced the Washington University researchers to continue those studies.

"Because PexRAP is downstream, it theoretically might cause fewer side effects, but nobody knows what role the protein might play in different tissues in the body," Semenkovich says. "We need to conduct more experiments with the goal that we may be able to move into some sort of clinical trials relatively soon. It's very important to find new treatments for obesity and diabetes because these disorders aren't just an inconvenience, both can be lethal."


Story Source:

The above story is based on materials provided by Washington University School of Medicine. The original article was written by Jim Dryden. Note: Materials may be edited for content and length.


Journal Reference:

  1. IrfanJ. Lodhi, Li Yin, AnneP.L. Jensen-Urstad, Katsuhiko Funai, Trey Coleman, JohnH. Baird, MeralK. ElRamahi, Babak Razani, Haowei Song, Fong Fu-Hsu, John Turk, ClayF. Semenkovich. Inhibiting Adipose Tissue Lipogenesis Reprograms Thermogenesis and PPARγ Activation to Decrease Diet-Induced Obesity. Cell Metabolism, 2012; DOI: 10.1016/j.cmet.2012.06.013

Cite This Page:

Washington University School of Medicine. "New target for treating diabetes and obesity." ScienceDaily. ScienceDaily, 2 August 2012. <www.sciencedaily.com/releases/2012/08/120802150435.htm>.
Washington University School of Medicine. (2012, August 2). New target for treating diabetes and obesity. ScienceDaily. Retrieved April 20, 2014 from www.sciencedaily.com/releases/2012/08/120802150435.htm
Washington University School of Medicine. "New target for treating diabetes and obesity." ScienceDaily. www.sciencedaily.com/releases/2012/08/120802150435.htm (accessed April 20, 2014).

Share This



More Health & Medicine News

Sunday, April 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Nine-Month-Old Baby Can't Open His Mouth

Nine-Month-Old Baby Can't Open His Mouth

Newsy (Apr. 19, 2014) Nine-month-old Wyatt Scott was born with a rare disorder called congenital trismus, which prevents him from opening his mouth. Video provided by Newsy
Powered by NewsLook.com
'Holy Grail' Of Weight Loss? New Find Could Be It

'Holy Grail' Of Weight Loss? New Find Could Be It

Newsy (Apr. 18, 2014) In a potential breakthrough for future obesity treatments, scientists have used MRI scans to pinpoint brown fat in a living adult for the first time. Video provided by Newsy
Powered by NewsLook.com
Little Progress Made In Fighting Food Poisoning, CDC Says

Little Progress Made In Fighting Food Poisoning, CDC Says

Newsy (Apr. 18, 2014) A new report shows rates of two foodborne infections increased in the U.S. in recent years, while salmonella actually dropped 9 percent. Video provided by Newsy
Powered by NewsLook.com
Scientists Create Stem Cells From Adult Skin Cells

Scientists Create Stem Cells From Adult Skin Cells

Newsy (Apr. 17, 2014) The breakthrough could mean a cure for some serious diseases and even the possibility of human cloning, but it's all still a way off. 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:
from the past week

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