Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Glowing fish shed light on metabolism

03.12.2012
UCSF scientists use tiny zebrafish to screen for drugs to help control obesity, diabetes, other conditions

A tiny, translucent zebrafish that glows green when its liver makes glucose has helped an international team of researchers identify a compound that regulates whole-body metabolism and appears to protect obese mice from signs of metabolic disorders.

Led by scientists at the University of California, San Francisco (UCSF), the work demonstrates how a fish smaller than a grain of rice can help screen for drugs to help control obesity, type 2 diabetes and other metabolic disorders, which affect a rising 34 percent of American adults and are major risk factors for cardiovascular disease.

Described this week in the journal Nature Chemical Biology, the new compound emerged from a panel of 2,400 medications and drug-like compounds tested in the zebrafish. The test was designed to identify key regulators of "fasting metabolism"— a state most people face every day after the lingering remnants of their long-digested meals pass slowly down their digestive tract.

Fasting metabolism is the body's way of fulfilling its energy needs between meals by turning to fat and other stored sources. It involves a carefully balanced and coordinated cascade of reactions that see numerous genes in various tissues kick into action and do things like burn fat.

In type 2 diabetes and other metabolic diseases, this careful balance is lost.

"The body cannot keep up with the breakdown of energy, and lipids [molecules of fat] can accumulate to toxic levels in the liver," said UCSF postdoctoral fellow Philipp Gut, MD, who led the research with Didier Y.R. Stainier, PhD, a professor in the Department of Biochemistry and Biophysics.

How the Screen Works

Some screens can be conducted in cell culture by taking living cells grown in the laboratory and exposing them to various drugs. The ability to rapidly test large libraries of compounds in the last few decades through such screens has revolutionized biomedical science.

But looking for drugs that regulate biological processes like metabolism, which involves multiple interacting organs in the body, and even more types of cells, cannot be done in cell screens because they lack the same complexity. Mice are often used to test pharmacological compounds, but screens of this magnitude would require thousands of mice, which would be ethically impossible to justify and prohibitively expensive.

Gut and his colleagues set out to develop the zebrafish screen as an ethical and inexpensive solution, and the new paper demonstrates the validity of this approach, he said. Furthermore, this study illustrates the fact that model organisms should be an integral part of the new roadmap defined by the NIH and other medical research organizations around the world to translate the most advanced laboratory science into benefits for patients, Stainier said.

Of the thousands of compounds the team screened, two appeared to turn on a handful of genes that caused the animals to burn fat as a way of producing energy – an end that would be desirable for many people with metabolic disorders.

Further experiments with one of these compounds in mice showed that it could protect obese mice from metabolic problems.

The article, "Whole-organism screening for gluconeogenesis identifies activators of fasting metabolism," by Philipp Gut, Bernat Baeza-Raja, Olov Andersson, Laura Hasenkamp, Joseph Hsiao, Daniel Hesselson, Katerina Akassoglou, Eric Verdin, Matthew D Hirschey and Didier Y R Stainier will be published online by the journal Nature Chemical Biology on Dec. 2, 2012.

This study was supported by the National Institutes of Health through grant #P30 DK026743, #P30 DK063720, #DK59637, #NS051470, #U01 DK089541 and #RO1 DK60322 and by a grant from the American Heart Association. Additional funds were provided by the Gladstone Institutes, the Glenn Foundation for Medical Research and through a postdoctoral fellowship from the German Research Foundation.

In addition to UCSF, authors on this study are associated with the Gladstone Institutes in San Francisco; Duke University Medical Center in Durham, N.C.; Karolinska Institutet in Stockholm, Sweden; the Garvan Institute of Medical Research in New South Wales, Australia; and the Max Planck Institute for Heart and Lung Research in Bad Nauheim, Germany.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

Jason Socrates Bardi | EurekAlert!
Further information:
http://www.ucsf.edu

More articles from Life Sciences:

nachricht How to become a T follicular helper cell
31.07.2015 | La Jolla Institute for Allergy and Immunology

nachricht Heating and cooling with light leads to ultrafast DNA diagnostics
31.07.2015 | University of California - Berkeley

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum Matter Stuck in Unrest

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...

Im Focus: On the crest of the wave: Electronics on a time scale shorter than a cycle of light

Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.

The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

Im Focus: Smarter window materials can control light and energy

Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.

By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

California 'rain debt' equal to average full year of precipitation

31.07.2015 | Physics and Astronomy

Telescopes team up to find distant Uranus-sized planet through microlensing

31.07.2015 | Physics and Astronomy

Quantum Matter Stuck in Unrest

31.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>