Reducing Cholesterol

Reported June 17, 2008

(Ivanhoe Newswire) Researchers have discovered a regulator that could lead to new therapies for lowering unhealthy levels of cholesterol and fats.

The team of scientists from the Harvard School of Public Health demonstrated that turning off the regulatory molecule – known as XBP1 – dramatically reduced blood levels of cholesterol and triglyceride fats in an animal model. There were also no apparent adverse effects on the liver.

“XBP1 may be an attractive drug target for treating dyslipidemias [excess fats in the blood],” said Laurie Glimcher, senior author of the report.

The researchers discovered XBP1 is activated by a high carbohydrate diet. It then turns on genes for enzymes that cause the liver to manufacture fat and fat-like substances, which are transported in the blood to fat tissue for storage. Excess amounts of cholesterol and triglycerides in the bloodstream can lead to heart disease and increased risk of strokes.

Working on mice models, the research team knew that XBPI was also a coordinator of a cell’s response to misaligned proteins and was necessary for normal development of a mouse fetus. After engineering a mechanism that could turn off XBP1 in adult mice, they discovered that “bad” LDL cholesterol in the mice blood stream was eliminated. At the same time the manufacture of triglycerides in the liver was also shut down.

The team concluded the XBP1 was playing a key role in fat manufacture that was independent of its role as a healthy protein coordinator. The hope is that researchers will be able to create drugs targeted to XBP1 that can safely control cholesterol and triglycerides.

Currently high cholesterol is treated with statin drugs which control cholesterol by inhibiting a key enzyme in the liver. But XBP1 may control both cholesterol and triglycerides and could provide a powerful treatment for reducing both without any adverse effects.

“We don’t know whether blocking the XBP1 pathway will be better than the statins which are very good drugs but have side effects like all drugs do,” said Glimcher.

SOURCE: Science June 13, 2008