Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern researchers discover role of two genes involved in cholesterol excretion

19.11.2002


Two specific genes involved in cholesterol transport are required for the most common way excess cholesterol is expelled from our bodies, according to scientists at UT Southwestern Medical Center at Dallas.



The genes, the researchers report, are essential for efficient secretion of cholesterol into the bile, which is the major route that cholesterol exits the body. The discovery sheds new light on potential therapies that could play an important role in reducing high cholesterol, a major risk factor of atherosclerotic diseases, such as coronary heart disease and stroke.

The new findings are reported in this week’s issue of the Proceedings of the National Academy of Sciences.


"The disruption of the two genes, Abcg5 and Abcg8, reveals their crucial role in biliary cholesterol secretion," said Dr. Liqing Yu, an instructor in the Eugene McDermott Center for Human Growth and Development and in molecular genetics and lead author of the study. "In humans and mice, the secretion of cholesterol into the bile is essential for maintaining cholesterol homeostasis and constitutes a major defense against the accumulation of dietary cholesterol in blood and tissues."

Dr. Helen Hobbs, senior author of the study, said, "By activating or upregulating Abcg5 and Abcg8 you could theoretically reduce cholesterol in the body by increasing cholesterol transport into the bile and limiting cholesterol absorption. This may also reduce cholesterol in the blood." Hobbs directs the Eugene McDermott Center for Human Growth and Development and the Donald W. Reynolds Cardiovascular Clinical Research Center. She also is an investigator in UT Southwestern’s Howard Hughes Medical Institute.

The researchers uncovered this critical pathway by studying mice that lacked the genes.

When researchers fed the mice high cholesterol diets, "We discovered that the fatty liver was developed due to a massive accumulation of cholesterol," Yu said. "We think this happens because the dietary cholesterol cannot be efficiently secreted into the bile, but it is accumulated in the liver and plasma when Abcg5 and Abcg8 are disrupted."

Liver and plasma cholesterol levels were increased by as much as 18-fold and 2.4-fold, respectively, in the mice after they ate a cholesterol-rich diet. Disruption of the two genes also resulted in a 30-fold increase in plasma levels of sitosterol, the major plant sterol, and a two- to threefold increase in fractional absorption of dietary plant sterols.

"Plant sterols are similar to cholesterol, structurally, and in the absence of Abcg5 and Abcg8 the compounds accumulate in the body, which leads to a rare inherited disease called sitosterolemia," Yu said. "Individuals with this disease have dramatically increased plasma plant sterol levels, which is associated with premature atherosclerotic coronary heart disease."

UT Southwestern researchers, in conjunction with researchers at Tularik Inc., discovered the two genes in 2000.

Before scientists identified the genes, the molecular mechanism by which dietary cholesterol is absorbed and the mechanisms by which cholesterol and other sterols are secreted into the bile were not known, Hobbs said.

"The actual discovery of the two genes in 2000 led to a better understanding of two important pathways of cholesterol metabolism," she said.


Other UT Southwestern researchers involved in the study were Dr. Jonathan Cohen, associate professor of internal medicine; Dr. Robert Hammer, professor of biochemistry; and Dr. Jia Li-Hawkins, now with Pfizer. Researchers from the University of Bonn in Germany also contributed.

The studies were supported by The Howard Hughes Medical Institute, the National Institutes of Health, the Perot Fund; the W. M. Keck Foundation; and the Donald W. Reynolds Cardiovascular Clinical Research Center.

To automatically receive news releases from UT Southwestern via e-mail, go to http://www3.utsouthwestern.edu/ and click on "Latest News." Then go to "Receive our News" to subscribe.

Amy Shields | EurekAlert!
Further information:
http://www.swmed.edu/
http://www3.utsouthwestern.edu

More articles from Life Sciences:

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>