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
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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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
Liquid Biopsies: Utilization of Circulating Biomarkers for Minimally Invasive Diagnostics Development
Market Trends in Biofluid-based Liquid Biopsies: Deploying Circulating Biomarkers in the Clinic. Enal Razvi, Ph.D., Managing Director, Select Biosciences, Inc.
Self-Assembling, Biomimetic Membranes May Aid Water Filtration
A synthetic membrane that self assembles and is easily produced may lead to better gas separation, water purification, drug delivery and DNA recognition, according to an international team of researchers.
Researchers Discover Immune System’s 'Trojan Horse'
Oxford University researchers have found that human cells use viruses as Trojan horses, transporting a messenger that encourages the immune system to fight the very virus that carries it.
How Cholesterol Leads to Clogged Arteries
A new study shows that when immune cells called neutrophils are exposed to cholesterol crystals, they release large extracellular web-like structures that trigger the production of inflammatory molecules linked to artherosclerosis.
Study Questions Presence in Blood of Heart-Healthy Molecules from Fish Oil Supplements
A new study from the Perelman School of Medicine at the University of Pennsylvania questions the relevance of fish oil-derived SPMs and their purported anti-inflammatory effects in humans.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Key Player in Diabetic Kidney Disease Revealed
Discovery could lead to new and better diagnostic marker for chronic kidney disease.
Can Cell Cycle Protein Prevent or Kill Breast Cancer Tumors?
An MD Anderson study has shown the potential of a simple molecule involved in cancer metabolism as a powerful therapeutic.
Study Reveals Improved Way to Interpret High-Throughput Biological Data
A recent study has revealed a novel workflow, identifying associations between molecules to provide insights into cellular metabolism and gene expression in complex biological systems.
Skyscraper Banner

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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!