Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Study identifies glucose 'sensor' that plays dual role in glucose metabolism and fat synthesis

27.12.2006
Findings point to possible new treatment target for obesity and diabetes

In the study, glucose is shown to stimulate the activity of the Liver X Receptors (LXR) a and b, The LXRs act as sensors of dietary components, orchestrating the body's response to nutrients such as oxysterols (short-lived derivatives of cholesterol) and controlling gene expression linked to cholesterol and fat metabolism.

"When you eat, glucose pours into the gut and is recognized by LXR in the liver, which then activates expression of the enzymes that turn excess glucose into triglycerides that are stored as fat," said Enrique Saez, a Scripps Research scientist who led the study. "The fact that our study demonstrates that LXR does both-it binds to glucose and it induces fatty acid synthesis-is significant and makes LXR a potential target for diabetes and obesity treatments."

In some recent animal studies, Saez pointed out, activation of LXRs using synthetic molecules also induced regression of atherosclerosis, the clogging, narrowing, and hardening of the body's large arteries and blood vessels that can lead to stroke, heart attack, and eye and kidney problems. Elevated levels of pathogenic cholesterols, also known to bind LXR, are a primary risk for development of atherosclerosis.

"The integration of glucose sensing and control of lipogenesis by LXR may explain why low-fat/high-carbohydrate diets induce hypertriglyceridemia [an elevated level of triglycerides in the blood]," Saez said. "LXR can sense surplus glucose, induce fatty acid synthesis, and prompt the liver's export of triglycerides into the bloodstream. Since LXR acts as the body's sensor of a buildup of pathogenic cholesterol, its ability to bind both glucose and oxysterols suggests that LXR may be a link between hyperglycemia and atherosclerosis."

In fact, Saez and his colleagues originally looked at LXR as a drug target for atherosclerosis. But when they fed synthetic LXR ligands to mice to induce activation, they discovered that the mice metabolized glucose more effectively and that activation suppressed new production of glucose in the liver.

That prompted the scientists to look more closely at glucose levels as the LXR activating mechanism in the liver.

To their surprise, what Saez and his colleagues discovered was that glucose bound directly to LXR. This was unexpected because the carbohydrate does not conform to the standard definition of a typical ligand that activates nuclear receptors, transcription factors that coordinate gene expression in response to hormonal and environmental signals. This discovery, Saez said, represents the first signaling pathway where a carbohydrate activates a nuclear receptor, although the precise mode of binding remains unknown.

As part of the study, mice were put on exclusive sucrose or D-glucose diets; all diets were devoid of cholesterol to minimize naturally occurring oxysterols. D-glucose and GW3965 (a synthetic LXR activator) induced similar changes in hepatic gene expression, indicating that LXR functions as a glucose sensor in vivo that responds to increasing liver glucose uptake. The ability of the LXRs to respond to glucose and its derivatives was very specific: no effect was seen in other nuclear receptors tested.

The current study focused primarily on the role of glucose sensing in the liver and gut. New studies will focus on the question of whether glucose levels in other tissue types, such as the pancreas, activate LXR, Saez added.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Studies and Analyses:

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

nachricht Disarray in the brain
18.12.2017 | Universität zu Lübeck

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: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Gran Chaco: Biodiversity at High Risk

17.01.2018 | Ecology, The Environment and Conservation

Only an atom thick: Physicists succeed in measuring mechanical properties of 2D monolayer materials

17.01.2018 | Physics and Astronomy

Fraunhofer HHI receives AIS Technology Innovation Award 2018 for 3D Human Body Reconstruction

17.01.2018 | Awards Funding

VideoLinks
B2B-VideoLinks
More VideoLinks >>>