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 WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

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: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

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...

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

Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal

22.05.2018 | Life Sciences

Asian tiger mosquito on the move

22.05.2018 | Life Sciences

Self-illuminating pixels for a new display generation

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>