Featured Research

from universities, journals, and other organizations

Breaking cycle of obesity, inflammation, disease

Date:
December 19, 2013
Source:
University of Michigan
Summary:
Researchers have illuminated an aspect of how the metabolic system breaks down in obesity. The findings provide additional evidence that a drug entering clinical trials could reverse obesity, Type 2 diabetes and fatty liver disease in humans.

Researchers at University of Michigan have illuminated an aspect of how the metabolic system breaks down in obesity. The findings provide additional evidence that a drug entering clinical trials at the university could reverse obesity, Type 2 diabetes and fatty liver disease in humans.

In a paper scheduled for online publication in the journal eLife on Dec. 24, Alan Saltiel, the Mary Sue Coleman Director of the Life Sciences Institute, explains how, in obesity, fat cells stop responding to hormones known as catecholamines that trigger them to expend more energy. However, the fat cells of obese mice treated with a drug called amlexanox regained sensitivity to catecholamines, burned the excess energy and returned to normal size.

Next month, scientists at U-M will begin a placebo-controlled clinical trial of amlexanox to test its efficacy as a drug for treating obesity and diabetes in humans. Formulations of amlexanox are prescribed in different international markets to treat asthma and canker sores.

Obesity leads to a state of chronic, low-grade inflammation in liver and fat tissue. Scientists believe that inflammation links obesity and insulin resistance via a pathway called NFkB, which is involved in the regulation of a range of cellular processes and activated in obesity.

Activation of NFkB increases the levels of a pair of genes, IKKε and TBK1, which in turn reduce the ability of certain receptors in the fat cells of obese mice to respond to catecholamines like adrenaline, "fat-burning" hormones generated by the sympathetic nervous system in response to stress.

"We've suspected that in obesity, fat cells become less sensitive to catecholamines such as adrenaline, and that this reduced sensitivity in turn reduces energy expenditure, but the details of this haven't been fully understood," Saltiel said.

High levels of IKKε and TBK1 also resulted in lower levels of a second messenger molecule called cAMP, which increases energy expenditure by elevating fat burning.

Amlexanox interfered with the two enzymes and restored sensitivity to catecholamine, allowing the fat cells to burn energy.

In research published in February 2013, Saltiel found that amlexanox reversed obesity, diabetes and fatty liver in mice. The forthcoming eLife paper explains in part how amlexanox works.

"There is considerable evidence to suggest that in states of obesity, adipose tissue becomes less sensitive to catecholamines because IKKε and TBK1 act as a sort of brake on metabolism, and that this reduced sensitivity in turn reduces energy expenditure," Saltiel said. "By releasing the brake, amlexanox seems to free the metabolic system of mice to burn more and possibly store less energy in response to catecholamines."


Story Source:

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


Journal Reference:

  1. J. Mowers, M. Uhm, S. M. Reilly, J. Simon, D. Leto, S.-H. Chiang, L. Chang, A. R. Saltiel. Inflammation produces catecholamine resistance in obesity via activation of PDE3B by the protein kinases IKK and TBK1. eLife, 2013; 2 (0): e01119 DOI: 10.7554/eLife.01119

Cite This Page:

University of Michigan. "Breaking cycle of obesity, inflammation, disease." ScienceDaily. ScienceDaily, 19 December 2013. <www.sciencedaily.com/releases/2013/12/131219125957.htm>.
University of Michigan. (2013, December 19). Breaking cycle of obesity, inflammation, disease. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2013/12/131219125957.htm
University of Michigan. "Breaking cycle of obesity, inflammation, disease." ScienceDaily. www.sciencedaily.com/releases/2013/12/131219125957.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Quintuplets Head Home

Texas Quintuplets Head Home

Reuters - US Online Video (Aug. 1, 2014) After four months in the hospital, the first quintuplets to be born at Baylor University Medical Center head home. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Patient Coming to U.S. for Treatment

Ebola Patient Coming to U.S. for Treatment

Reuters - US Online Video (Aug. 1, 2014) A U.S. aid worker infected with Ebola while working in West Africa will be treated in a high security ward at Emory University in Atlanta. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. 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