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 A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

nachricht CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

Im Focus: Optoelectronic Inline Measurement – Accurate to the Nanometer

Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.

New Manufacturing Technologies for New Products

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

A new technique isolates neuronal activity during memory consolidation

22.06.2017 | Life Sciences

Plant inspiration could lead to flexible electronics

22.06.2017 | Materials Sciences

A rhodium-based catalyst for making organosilicon using less precious metal

22.06.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>