Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers develop new model for understanding obesity, diabetes

14.01.2003


Through the study of fat storage in nematode worms, researchers at UT Southwestern Medical Center at Dallas have formulated a new model for understanding the mechanisms of obesity and diabetes in humans.



Their work appears in today’s issue of Developmental Cell.

"Obesity and its associated diseases are now among the most important medical conditions in the world," said Dr. Jonathan M. Graff, senior author of the study and associate professor in the Center for Developmental Biology.


"A billion people in the world are overweight, and during the next few decades, it will be one of the major health issues facing mankind. The alarming increase in obesity highlights the critical need to identify genes that are involved in regulating fat-cell development and function," he said.

Approximately 58 million Americans are overweight, and about 300,000 deaths annually are attributable to poor diet and inactivity, according to the National Institute of Diabetes and Digestive and Kidney Diseases. Nearly 70 percent of cardiovascular disease cases are related to obesity.

The American Diabetes Association reports about 17 million people suffer from diabetes, a disease in which the body does not produce or properly use insulin. In fact, it was the sixth-leading cause of death listed on U.S. death certificates in 1999.

To understand the genetic processes regulating fat biology, UT Southwestern researchers generated nematode worms (Caenorhabditis elegans) lacking two genes crucial for fat in mammals. Worms deficient in either gene displayed a lipid-depleted phenotype – pale, skinny, larval-arrested and lacking fat stores, said Graff.

"Our hypothesis was that the same or related genes would control fat storage in worms and mammals," Graff said. "We took a couple of the genes thought to be among the most important ones that control fat formation in mammals and eliminated their function in the worms. Notably, the worms did not accumulate fat; therefore, the worms appear to be a good model for fat biology, which opens the possibility that they can be exploited to improve human health."

Using this phenotype, a genetic screen then identified many additional genes that are necessary for fat accumulation in worms, Graff said.

"Several of the genes that we found had never been identified, and 90 percent of the discovered genes are also present in humans," Graff said. "Two of them are related to human fat diseases, and three we tested are required in mammalian models to generate fat. This small ancient organism with very few cells and relatively few genes seems to use many of the same genes as humans. We’ve established it as a model, we’ve found more genes, and now we’re trying to link them to human biology."

Two of these genes encode components of the mitochondrial respiratory chain (biochemical processes in the mitochondria that produce energy), and when the chain was inhibited chemically in the worms or a mammalian fat-cell model, fat accumulation was markedly reduced. Gene mutations in the mitochondrial respiratory chain already have been linked to abnormalities in fat accumulation in humans, including lipodystrophy (a metabolic disorder causing changes in body fat).

Another protein that the team identified is present in human fat and required for fat storage in mammals.

Through this worm study, scientists now have crucial data toward developing therapeutics for lipodystrophy and other disorders, including obesity and diabetes.

"Because of the explosion of obesity and diabetes, there has been a huge amount of work to find the genes involved, but researchers really have not exploited the power of genetics," Graff said. "So, the identification of an appropriate invertebrate genetic model system might hasten the discovery of new genes important in fat biology. That is, the worms provide a platform to rapidly identify key proteins that regulate formation of fat, some of which might be targets for new therapies to treat obesity or diabetes."

Further, the research reinforces C. elegans as a tool in learning about the mechanisms that trigger the biology of fat-storing tissues. This is important because the worms are an inexpensive, rapid way to conduct accurate research, said Dr. Leon Avery, associate professor of molecular biology and a study author. C. elegans’ generation time is four days, and 100,000 worms can fit on a small petri plate.

"There’s been good work on the control of fat accumulation in mammals for many years, but there hasn’t been a good model organism system," Avery said. "So, the field has been, so to speak, hopping along on one leg. The work on fat accumulation in worms establishes C. elegans as a model organism in which this problem can be studied, and thus supplies the other leg."

Contact: Scott Maier
e-mail: scott.maier@utsouthwestern.edu

Scott Maier | EurekAlert!

More articles from Health and Medicine:

nachricht Study shows novel protein plays role in bacterial vaginosis
13.12.2019 | University of Arizona Health Sciences

nachricht Illinois team develops first of a kind in-vitro 3D neural tissue model
12.12.2019 | University of Illinois College of Engineering

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Virus multiplication in 3D

Vaccinia viruses serve as a vaccine against human smallpox and as the basis of new cancer therapies. Two studies now provide fascinating insights into their unusual propagation strategy at the atomic level.

For viruses to multiply, they usually need the support of the cells they infect. In many cases, only in their host’s nucleus can they find the machines,...

Im Focus: Cheers! Maxwell's electromagnetism extended to smaller scales

More than one hundred and fifty years have passed since the publication of James Clerk Maxwell's "A Dynamical Theory of the Electromagnetic Field" (1865). What would our lives be without this publication?

It is difficult to imagine, as this treatise revolutionized our fundamental understanding of electric fields, magnetic fields, and light. The twenty original...

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Supporting structures of wind turbines contribute to wind farm blockage effect

13.12.2019 | Physics and Astronomy

Chinese team makes nanoscopy breakthrough

13.12.2019 | Physics and Astronomy

Tiny quantum sensors watch materials transform under pressure

13.12.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>