Featured Research

from universities, journals, and other organizations

Molecular 'firing squad' in mice triggered by overeating destroys metabolism

Date:
February 5, 2010
Source:
Harvard School of Public Health
Summary:
Overeating in mice triggers a molecule once considered to be only involved in detecting and fighting viruses to also destroy normal metabolism, leading to insulin resistance and setting the stage for diabetes.

Overeating in mice triggers a molecule once considered to be only involved in detecting and fighting viruses to also destroy normal metabolism, leading to insulin resistance and setting the stage for diabetes. The new study, led by researchers at the Harvard School of Public Health (HSPH), specifically links together the immune system and metabolism, a pairing increasingly suspected in diseases that include -- in addition to diabetes -- heart disease, fatty liver, cancer, and stroke.

Understanding how to regulate the molecule through targeted drugs or nutrients could eventually change the way these diseases are prevented and treated in humans.

The study will publish in the February 5, 2010, issue of Cell.

"When mice eat a normal diet, this molecule called PKR is silent," said senior author Gφkhan Hotamisligil, chair of the HSPH Department of Genetics and Complex Diseases. "However, if a cell containing PKR is bombarded with too many nutrients, PKR grabs other immune system molecules that respond to this food attack and organizes a firing squad to shoot down normal processes, leading to insulin resistance and metabolic dysfunction."

The results provide compelling evidence that a process called "metaflammation" occurs in the body, said Hotamisligil. Metaflammation is inflammation triggered by the metabolism of nutrients that occurs when the body processes food into energy. Previous studies by Hotamisligil had demonstrated inflammation in metabolic diseases such as obesity, type 2 diabetes, and heart disease in mice and humans.

"We know that nutrients can be detrimental in excess quantities or when they are in the wrong place at the wrong time," Hotamisligil said. "But we don't quite understand which paths they travel that result in harm and produce inflammation. PKR is a mechanism by which nutrients -- necessary and beneficial under normal conditions -- cause damage to cells and organs."

The researchers used sets of mice in their experiments. One set had PKR in its bodies, and the other set did not. The scientists then overfed a group of PKR-positive and PKR-negative mice high-fat, high-calorie diets. The overfed mice with PKR became obese and developed insulin resistance, while the overfed mice without PKR gained significantly less weight and did not develop insulin resistance, indicating that absence of PKR can alleviate harmful metabolic effects due to overeating in mice.

Now the researchers will turn their attention to identifying which nutrients cause the adverse effects. "One of the difficulties in understanding how our diet is integrated into disease risk is our inability to understand what specific component of a diet is actually regulating particular responses in humans," said Hotamisligil. "So the discovery of this molecule actually gives us a very specific way to identify the harmful components of the diet."

Results from those studies could be available within a couple of years, Hotamisligil predicted, after which human trials would be needed on potential drugs or nutrients that could regulate PKR.

This study was supported by a grant from the National Institutes of Health. The first author was Takahisa Nakamura, a research fellow in the HSPH Department of Genetics and Complex Diseases who was supported by a Human Frontier Science Program Fellowship Award and the Uehara Memorial Foundation. Other co-authors are supported by fellowships from the Japan Society for the Promotion of Science and the American Diabetes Association.


Story Source:

The above story is based on materials provided by Harvard School of Public Health. Note: Materials may be edited for content and length.


Journal Reference:

  1. Takahisa Nakamura, Masato Furuhashi, Ping Li, Haiming Cao, Gurol Tuncman, Nahum Sonenberg, Cem Gorgun, and Gφkhan Hotamisligil. Double-stranded RNA-dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell, February 5, 2010

Cite This Page:

Harvard School of Public Health. "Molecular 'firing squad' in mice triggered by overeating destroys metabolism." ScienceDaily. ScienceDaily, 5 February 2010. <www.sciencedaily.com/releases/2010/02/100204144429.htm>.
Harvard School of Public Health. (2010, February 5). Molecular 'firing squad' in mice triggered by overeating destroys metabolism. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2010/02/100204144429.htm
Harvard School of Public Health. "Molecular 'firing squad' in mice triggered by overeating destroys metabolism." ScienceDaily. www.sciencedaily.com/releases/2010/02/100204144429.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) — Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) — A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. 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