Featured Research

from universities, journals, and other organizations

Researchers Identify Link Between Obesity And Type 2 Diabetes

Date:
January 18, 2002
Source:
Beth Israel Deaconess Medical Center
Summary:
Researchers at Beth Israel Deaconess Medical Center (BIDMC) have identified a mechanism that helps explain how the hormone leptin acts to metabolize fatty acids in muscle, establishing for the first time a novel molecular link between obesity and diabetes, and creating the possibility of a new target for the development of drugs to help manage both conditions.

BOSTON – Researchers at Beth Israel Deaconess Medical Center (BIDMC) have identified a mechanism that helps explain how the hormone leptin acts to metabolize fatty acids in muscle, establishing for the first time a novel molecular link between obesity and diabetes, and creating the possibility of a new target for the development of drugs to help manage both conditions. The study appears in the Jan. 17 issue of the journal Nature.

Discovered in 1994, leptin first gained widespread attention as a “satiety signal” or appetite suppressant. Initial studies revealed that the hormone, which is produced in fat cells, travels through the bloodstream and interacts with receptors in the brain to provide a “signal” that the body has consumed enough food and should stop eating.

Since then, however, scientists have demonstrated that leptin's role is not confined to suppressing appetite. Leptin receptors have also been identified in the T-cells of the immune system and in new blood vessels, and, as this new research suggests, the hormone has also been shown to play an important role in metabolism. “Leptin is a master regulator of our bodies’ hormonal systems,” explains Barbara Kahn, M.D., Chief of Endocrinology at Beth Israel Deaconess and Professor of Medicine at Harvard Medical School. “It probably evolved as a regulator that could be suppressed to protect people and animals when no food was available.” Kahn served as the study's senior author. BIDMC researcher Yasuhiko Minokoshi, M.D., Ph.D., is the first author. Impaired fuel metabolism is a well-known factor in obesity as well as type 2 diabetes. When fatty acids in muscle and the liver are not sufficiently utilized, their buildup not only impairs the body’s ability to burn calories, but also leads to insulin resistance, which increases a person's risk of developing diabetes. This new research focuses on the enzyme 5’-AMP activated protein kinase (AMPK), a molecule that had previously been identified as a “fuel gauge” which acts on key enzymes in both cholesterol metabolism and glycogen synthesis. Kahn and her colleagues hypothesized that AMPK might also be serving as a “signaling pathway” for leptin, enabling the hormone to metabolize fatty acids in muscle.

To test their hypothesis, the researchers injected laboratory mice with leptin. They discovered that the hormone was indeed activating AMPK in muscle when administered either directly into a peripheral vein or into the brain's hypothalamus. This novel effect was the same in experiments conducted outside the body, when muscle was removed from the mice and incubated with leptin. In addition, by blocking the nerves to the animals’ legs, the researchers showed that leptin was exerting an indirect effect on muscle by way of the brain and sympathetic nervous system.

These results demonstrated that while there was an early activation of AMPK that resulted from leptin’s direct effect on skeletal muscle, later, more sustained, activation was indirectly taking place via the central nervous system. “We discovered that leptin, by way of AMPK, was inhibiting another enzyme, acetylCoA carboxylase (ACC), which had the result of increasing fat metabolism,” explains Kahn. Together with results of an earlier study showing that mice grew very lean when the ACC enzyme was removed, these findings suggest that the AMPK pathway could be a particularly promising target for drug treatments for obesity and diabetes.

“AMPK is a heterotrimeric enzyme,” Kahn adds. “This means that it contains three sections, alpha, beta and gamma, each of which contains two or three isoforms. Our study showed that a single isoform – alpha 2 – is the key to leptin's effects on fatty acid oxidation in muscle.” This finding is important, she emphasizes, because the greater the degree of molecular specificity, the greater the likelihood of success in developing new drugs without adverse side effects.

The incidence of obesity and type 2 diabetes has escalated tremendously over the past decade. A new report from the U.S. Surgeon General finds that 61 percent of American adults currently meet the scientific definition of “overweight” or “obese,” putting them at risk of developing type 2 diabetes, one of the leading causes of death and disability in this country. Diabetes affects 16 million individuals throughout the United States, and can lead to heart attack, stroke, atherosclerosis and peripheral blood vessel disease, among other serious conditions. “Since the discovery of leptin, we’ve known that it's a fascinating and important hormone,” says Kahn. “Now we know that the AMPK pathway is a key mechanism for leptin’s effects to mobilize fatty acids rather than deposit them. This provides important clues to help reduce the likelihood that obese patients will develop diabetes, and may lead to ways to reduce insulin resistance and its accompanying cardiovascular morbidity in people with diabetes and obesity.”

Study co-authors include Young-Bum Kim, Ph.D., Odile D. Peroni, Ph.D., and Corinna Muller, of Beth Israel Deaconess Medical Center, and Lee G. D. Fryer, Ph.D., and David Carling, Ph.D., of Hammersmith Hospital, London.

The study was funded by grants from the National Institutes of Health (NIH).

Beth Israel Deaconess Medical Center is a major patient care, research and teaching affiliate of Harvard Medical School and a founding member of CareGroup Healthcare System. Beth Israel Deaconess is the fourth largest recipient of National Institutes of Health research funding among independent U.S. hospitals.


Story Source:

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


Cite This Page:

Beth Israel Deaconess Medical Center. "Researchers Identify Link Between Obesity And Type 2 Diabetes." ScienceDaily. ScienceDaily, 18 January 2002. <www.sciencedaily.com/releases/2002/01/020117073521.htm>.
Beth Israel Deaconess Medical Center. (2002, January 18). Researchers Identify Link Between Obesity And Type 2 Diabetes. ScienceDaily. Retrieved September 2, 2014 from www.sciencedaily.com/releases/2002/01/020117073521.htm
Beth Israel Deaconess Medical Center. "Researchers Identify Link Between Obesity And Type 2 Diabetes." ScienceDaily. www.sciencedaily.com/releases/2002/01/020117073521.htm (accessed September 2, 2014).

Share This




More Health & Medicine News

Tuesday, September 2, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Get on Your Bike! London Cycling Popularity Soars Despite Danger

Get on Your Bike! London Cycling Popularity Soars Despite Danger

AFP (Sep. 1, 2014) Wedged between buses, lorries and cars, cycling in London isn't for the faint hearted. Nevertheless the number of people choosing to bike in the British capital has doubled over the past 15 years. Duration: 02:27 Video provided by AFP
Powered by NewsLook.com
Can You Train Your Brain To Eat Healthy?

Can You Train Your Brain To Eat Healthy?

Newsy (Sep. 1, 2014) New research says if you condition yourself to eat healthy foods, eventually you'll crave them instead of junk food. Video provided by Newsy
Powered by NewsLook.com
We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 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:
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