Featured Research

from universities, journals, and other organizations

Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity

Date:
September 4, 2009
Source:
University of Michigan
Summary:
Researchers have identified a gene that acts as a master switch to control obesity in mice. When the switch is turned off, even high-fat-diet mice remain thin.

Both mice were fed high-fat diets for several months. Deleting the IKKE gene in the mouse on the left protected it against the weight gain apparent in the mouse on the right.
Credit: Photo by Scott Galvin, U-M Photo Services

University of Michigan researchers have identified a gene that acts as a master switch to control obesity in mice. When the switch is turned off, even high-fat-diet mice remain thin.

Deleting the gene, called IKKE, also appears to protect mice against conditions that, in humans, lead to Type 2 diabetes, which is associated with obesity and is on the rise among Americans, including children and adolescents.

If follow-up studies show that IKKE is tied to obesity in humans, the gene and the protein it makes will be prime targets for the development of drugs to treat obesity, diabetes and complications associated with those disorders, said Alan Saltiel, the Mary Sue Coleman Director of the U-M Life Sciences Institute.

"We've studied other genes associated with obesity – we call them 'obesogenes' – but this is the first one we've found that, when deleted, stops the animal from gaining weight," said Saltiel, senior author of a paper to be published in the Sept. 4 edition of the journal Cell.

"The fact that you can disrupt all the effects of a high-fat diet by deleting this one gene in mice is pretty interesting and surprising," he said.

Obesity is associated with a state of chronic, low-grade inflammation that leads to insulin resistance, which is usually the first step in the development of Type 2 diabetes. In the Cell paper, Saltiel and his colleagues show that deleting, or "knocking out," the IKKE gene not only protected high-fat-diet mice from obesity, it prevented chronic inflammation, a fatty liver and insulin resistance, as well.

The high-fat-diet mice were fed a lard-like substance with 45 percent of its calories from fat. Control mice were fed standard chow with 4.5 percent of its calories from fat. The dietary regimen began when the mice were 8 weeks old and continued for 14 to 16 weeks.

The gene IKKE produces a protein kinase also known as IKKE. Protein kinases are enzymes that turn other proteins on or off. The IKKE protein kinase appears to target proteins which, in turn, control genes that regulate the mouse metabolism.

When the high-fat diet is fed to a normal mouse, IKKE protein-kinase levels rise, the metabolic rate slows, and the animal gains weight. In that situation, the IKKE protein kinase acts as a brake on the metabolism.

Knockout mice placed on the high-fat diet did not gain weight, apparently because deleting the IKKE gene releases the metabolic brake, allowing it to speed up and burn more calories, instead of storing those calories as fat.

"The knockout mice are not exercising any more than the control mice used in the study. They're just burning more energy," Saltiel said. "And in the process, they're generating a little heat, as well – their body temperature actually increases a bit."

Saltiel's team is now searching for small molecules that block IKKE protein-kinase activity. IKKE inhibitors could become candidates for drug development.

"If you find an inhibitor of this protein kinase, you should be able to obtain the same effect as knocking out the gene. And that's the goal," Saltiel said. If successful candidates are identified and drug development is pursued, a new treatment for obesity and diabetes is likely a decade away, he said.

First author of the Cell paper is Shian-Huey Chiang of the Life Sciences Institute. Co-authors are U-M researchers Merlijn Bazuine, Carey Lumeng, Lynn Geletka, Jonathan Mowers, Nicole White, Jing-Tyan Ma, Jie Zhou, Nathan Qi, Dan Westcott and Jennifer Delproposto. Timothy Blackwell and Fiona Yull of the Vanderbilt University School of Medicine also are co-authors.

The research was funded by the National Institutes of Health and the American Diabetes Association. All animal use was conducted in compliance with the Institute of Laboratory Animal Research's Guide for the Care and Use of Laboratory Animals and was approved by the University Committee on Use and Care of Animals at the University of Michigan.


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. Shian-Huey Chiang, Merlijn Bazuine, Carey N. Lumeng, Lynn M. Geletka, Jonathan Mowers, Nicole M. White, Jing-Tyan Ma, Jie Zhou, Nathan Qi, Dan Westcott, Jennifer B. Delproposto, Timothy S. Blackwell, Fiona E. Yull, Alan R. Saltiel. The Protein Kinase IKKɛ Regulates Energy Balance in Obese Mice. Cell, 2009; DOI: 10.1016/j.cell.2009.06.046

Cite This Page:

University of Michigan. "Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity." ScienceDaily. ScienceDaily, 4 September 2009. <www.sciencedaily.com/releases/2009/09/090903163719.htm>.
University of Michigan. (2009, September 4). Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2009/09/090903163719.htm
University of Michigan. "Mice Can Eat 'Junk' And Not Get Fat: Researchers Find Gene That Protects High-fat-diet Mice From Obesity." ScienceDaily. www.sciencedaily.com/releases/2009/09/090903163719.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Costs Keep Mounting

Ebola Costs Keep Mounting

Reuters - Business Video Online (Sep. 23, 2014) The WHO has warned up to 20,000 people could be infected with Ebola over the next few weeks. As Sonia Legg reports, the implications for the West African countries suffering from the disease are huge. Video provided by Reuters
Powered by NewsLook.com
Ebola Cases Could Reach 1.4 Million Within 4 Months

Ebola Cases Could Reach 1.4 Million Within 4 Months

Newsy (Sep. 23, 2014) Health officials warn that without further intervention, the number of Ebola cases in Liberia and Sierra Leone could reach 1.4 million by January. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Cases to Triple in Weeks Without Drastic Action

WHO: Ebola Cases to Triple in Weeks Without Drastic Action

AFP (Sep. 23, 2014) The number of Ebola infections will triple to 20,000 by November, soaring by thousands every week if efforts to stop the outbreak are not stepped up radically, the WHO warned in a study on Tuesday. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
5 Ways Men Can Prevent Most Heart Attacks

5 Ways Men Can Prevent Most Heart Attacks

Newsy (Sep. 23, 2014) No surprise here: A recent study says men can reduce their risk of heart attack by maintaining a healthy lifestyle, which includes daily exercise. 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:

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