Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Penn Study Shows Liver Receptor Key To Diet-Dependent Differences in Blood Lipid Levels

13.05.2005


Receptor Can, When Overly Abundant, Adjust for the Consequences of a High-Fat Diet

Researchers at the University of Pennsylvania School of Medicine have discovered that a molecule found in liver cells is an important link in explaining the relationship among diet, lipid levels in blood, and atherosclerosis. The research team surmises that drugs targeted at the liver may one day help lower elevated lipids and battle cardiovascular disease. Mitchell Lazar, MD, PhD, Director of the Institute for Diabetes, Obesity, and Metabolism at Penn, and colleagues report their findings in the May 2005 issue of Cell Metabolism.
The high-cholesterol, high-fat so-called “Western diet” has accelerated an epidemic of atherosclerotic cardiovascular disease, the leading cause of death in industrialized nations. And, understanding interactions between genes and the reality of what most people eat are increasingly recognized as critical for effective treatment.


Molecules found in the nucleus of liver cells called LXRs (for Liver X Receptors) have emerged in the last few years as crucial regulators of cholesterol and lipid metabolism. (Click on thumbnail to view full-size image). “The conventional wisdom–borne out of drug-development studies done before this paper–was that LXRs are good in terms of decreasing atherosclerosis and bad in terms of increased triglycerides,” explains Lazar. Indeed, although LXR-based experimental drugs, which dramatically increase LXR activity throughout the body, reduce cholesterol levels in the blood, they also lead to high levels of triglycerides.

Surmising that a targeted approach might work better, the researchers used transgenic mice engineered to have an excess of LXR in their liver only, which gave the mice high levels of cholesterol and an increased risk of heart disease. They found that LXR, which senses fat in the liver, could adjust the consequences of eating a high-fat Western diet.

The team found that the increased liver LXR worsened levels of cholesterol and triglycerides in mice fed a normal, low-fat diet. However, surprisingly, when the same transgenic mice with increased LXR were fed a high-fat/high-cholesterol diet, similar in composition to a standard Western diet, their blood cholesterol and triglyceride levels actually improved. Furthermore, the mice were protected from the atherosclerotic cardiovascular disease that normally results from this diet. However, the beneficial effect of the increased LXR levels was lost when mice were treated with the experimental drug.

The researchers concluded that increased expression of LXR in the liver is beneficial in a body full of natural molecules that bind to the LXR receptor, which are generated by the Western diet, but not when on a low-fat, healthy diet. However, this benefit is lost when a potent drug is added to the system. “The reason is that a different set of target genes is turned on by this synthetic molecule, as opposed to the natural molecule,” says Lazar. “We’re saying, maybe what we need are drugs that mimic the natural ligand rather than a sledgehammer like the potent pharmaceutical drugs that too powerfully activate LXRs throughout the body.” The hope is that these will decrease cholesterol without increasing triglycerides.

One of the main questions facing the study of complex metabolic diseases is, if two people eat a high-fat diet, why does one person’s cholesterol go up but the other’s does not. “If we find natural variations in people in the amount of LXR in their livers, this may help explain this conundrum of the difference in susceptibility to high cholesterol and heart disease, depending on diet,” says Lazar. “The answer is genetics. Our work suggests that one of the new genetic factors to pay attention to is the amount of LXR in the liver.”

The study was funded in part by the National Institutes of Health and a Bristol Myers Squibb Freedom to Discover Award in Metabolic Research. Study co-authors are Michael Lehrke, Corinna Lebherz, Segan Millington, Hong-Ping Guan, John Millar, Daniel J. Rader, and James M. Wilson, all from Penn.

Karen Kreeger | EurekAlert!
Further information:
http://www.uphs.upenn.edu

More articles from Studies and Analyses:

nachricht Physics of bubbles could explain language patterns
25.07.2017 | University of Portsmouth

nachricht Obstructing the ‘inner eye’
07.07.2017 | Friedrich-Schiller-Universität Jena

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

Getting closer to porous, light-responsive materials

26.07.2017 | Materials Sciences

Large, distant comets more common than previously thought

26.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>