Liver X Receptor: A Dual Role Glucose Sensor

Filed in archive Diagnostics , Studies , Treatment on December 30, 2006

Imagine a glucose-activated sensor that acts as a switch to decrease production of endogenous glucose in the liver, and increase conversion of glucose to fat for storage in adipose tissue. Wouldn't that be just the kind of device that diabetics are dreaming of?

That kind of sensor - called Liver X Receptor - have been first described by scientists at the Scripps Research Institute which could also have big implications for other conditions like heart disease and stroke.

In this particular Scripps study, glucose was shown to stimulate the activity of the Liver X Receptors (LXR) a and b: The LXRs being the sensors of dietary components, determining the body's response to nutrients like oxysterols (short-lived derivatives of cholesterol) and controlling gene expression linked to cholesterol and fat metabolism.

According to Enrique Saez, Scripps Research scientist and the study's leader:

"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. 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.

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].

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."

While the current study focused 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.

This study, supported by the Genomics Institute of the Novartis Research Foundation was published December 20 in an advanced, online edition of Nature.

Read the full report at Scripps Research Institute.