Corporate Banner
Satellite Banner
Metabolomics & Lipidomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Researchers Engineer Metabolic Pathway in Mice to Prevent Diet-Induced Obesity

Published: Tuesday, June 09, 2009
Last Updated: Tuesday, June 09, 2009
Bookmark and Share
Researchers have constructed a non-native pathway in mice that increased fatty acid metabolism and resulted in resistance to diet-induced obesity.

In recent years, obesity has taken on epidemic proportions in developed nations, contributing significantly to major medical problems, early death and rising health care costs. According to Centers for Disease Control and Prevention estimates, at least a quarter of all American adults and more than 15 percent of children and adolescents are obese.

While recent research advances and treatment methods have had little effect in reducing obesity levels, researchers at the UCLA Henry Samueli School of Engineering and Applied Science, in collaboration with the David Geffen School of Medicine at UCLA, may have discovered a completely new way to approach the problem.

In a study to be published in the June 3 issue of the journal Cell Metabolism, chemical and biomolecular engineering professor James Liao, associate professor of human genetics and pediatrics Katrina Dipple and their research team demonstrate how they successfully constructed a non-native pathway in mice that increased fatty acid metabolism and resulted in resistance to diet-induced obesity.

"When we looked at the fatty-acid metabolism issue, we noted there are two aspects of the problem that needed to be addressed," Liao said. "One is the regulation; fatty acid metabolism is highly regulated. The other is digestion of the fatty acid; there needs to be a channel to burn this fat."

"We came up with an unconventional idea which we borrowed from plants and bacteria," said Jason Dean, a graduate student on Liao's team and an author of the study. "We know plants and bacteria digest fats differently from humans, from mammals. Plant seeds usually store a lot of fat. When they germinate, they convert the fat to sugar to grow. The reason they can digest fat this way is because they have a set of enzymes that's uniquely present in plants and bacteria. These enzymes are called the 'glyoxylate shunt' and are missing in mammals."

To investigate the effects of the glyoxylate shunt on fatty acid metabolism in mammals, Liao's team cloned bacteria genes from Escherichia coli that would enable the shunt, then introduced the cloned E. coli genes into the mitochondria of liver cells in mice; mitochondria are where fatty acids are burned in cells.

The researchers found that the glyoxylate shunt cut the energy-generating pathway of the cell in half, allowing the cell to digest the fatty acid much faster than normal. They also found that by cutting through this pathway, they created an additional pathway for converting fatty acid into carbon dioxide. This new cycle allowed the cell to digest fatty acid more effectively.

"The significance of this is great. It is a unique approach to understanding metabolism. Perturbing metabolic pathways, such as introducing the glyoxylate shunt and seeing how it affects overall metabolism, is a novel way to understand the control of metabolism," Dipple said.

The team also found that the new pathway decreased the regulatory signal malonyl-CoA. When malonyl-CoA levels are high, a signal is released that tells the body it is too full and that it needs to stop using fat and begin making it. Malonyl-CoA is high after eating a meal, blocking fatty acid metabolism. The new pathway, however, allowed for fat degradation even when the body was full.

Ultimately, the research team found that mice with the glyoxylate shunt that were fed the same high-fat diet - 60 percent of calories from fat - for six weeks remained skinny, compared with mice without the shunt.

"One exciting aspect of this study is that it provides a proof-of-principle for how engineering a specific metabolic pathway in the liver can affect the whole body adiposity and response to a high-fat diet," said Karen Reue, a UCLA professor of human genetics and an author of the study. "This could have relevance in understanding, and potentially treating, human obesity and associated diseases, such as diabetes and heart disease."

"We are very hopeful," said Liao. "This is the first example of how people can build new genes into mammals to achieve a desired function. It's very exciting that we've been able to achieve this new pathway in mammals that could potentially be used to fight a very serious problem."


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Disabling Enzyme Cripples Tumors, Cancer Cells
Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors.
Thursday, September 05, 2013
Key Protein is Linked to Circadian Clocks, Helps Regulate Metabolism
Study sheds light on molecular basis for metabolic health and disease.
Wednesday, June 19, 2013
Gene Mutation Gives Boost to Brain Cancer Cells
An international team of researchers has found that a singular gene mutation helps brain cancer cells to not just survive, but grow tumors rapidly.
Monday, June 10, 2013
Snails and Humans Use Same Genes to Tell Right from Left
Biologists have tracked down genes that control the handedness of snail shells, and they turn out to be similar to the genes used by humans to set up the left and right sides of the body.
Monday, December 29, 2008
Scientific News
Cancer Cells Kill Off Healthy Neighbours
Cancer cells create space to grow by killing off surrounding healthy cells, according to UK researchers working with fruit flies.
Future of Medicine Could be Found in a Tiny Crystal Ball
A Drexel University materials scientist has discovered a way to grow a crystal ball in a lab. Not the kind that soothsayers use to predict the future, but a microscopic version that could be used to encapsulate medication in a way that would allow it to deliver its curative payload more effectively inside the body.
Toxicity Testing With Cultured Liver Cells
Microreactor replaces animal testing.
Proteins Seek, Attack, Destroy Tumor Cells in Bloodstream
Using white blood cells to ferry potent cancer-killing proteins through the bloodstream virtually eliminates metastatic prostate cancer in mice, Cornell researchers have confirmed.
Why Do Some Infections Persist?
In preparing for the possibility of an antibiotic onslaught, some bacterial cultures adopt an all-for-one/one-for-all strategy that would make a socialist proud, University of Vermont researchers have found.
Flipping Molecular 'Switch' May Reduce Nicotine's Effects in the Brain
Scientists at The Scripps Research Institute (TSRI) have discovered that a lipid (fat molecule) in brain cells may act as a “switch” to increase or decrease the motivation to consume nicotine.
TSRI Team Comes Together with Rare Disease Community
Don’t worry, science fiction fans, the machines aren’t taking over quite yet. It turns out humans still beat computers at reading and comprehending text.
Magnesium Intake May Reduce Pancreatic Cancer Risk
Indiana University researchers have found that magnesium intake may be beneficial in preventing pancreatic cancer.
Gut Microbes: Burning Calories While You Sleep?
Study links changes in gut bacteria to lower resting metabolic rate and weight gain in mice.
Cooperating Bacteria Isolate Cheaters
Bacteria, which reciprocally exchange amino acids, stabilize their partnership on two-dimensional surfaces and limit the access of non-cooperating bacteria to the exchanged nutrients.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!