Molecule Could Hold Key to Cholesterol

Discovery of blood vessel compound may lead to better treatments, scientists say

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HealthDay Reporter

TUESDAY, April 3, 2007 (HealthDay News) -- A newly discovered molecule could lead to a whole new way of fighting high blood fats such as triglycerides and cholesterol, researchers say.

The molecule, abbreviated as GPIHBP1, sits on the surface of the endothelium, the delicate lining of blood vessels. It captures molecular particles called chylomicrons, which then deliver fats called triglycerides to cells that use them as fuel.

"We suspect that GPIHBP1 mutations will eventually be uncovered in humans with inherited forms of hyperlipidemia [high blood cholesterol levels]," said lead researcher Anne Beigneux, an assistant investigator at the University of California, Los Angeles, David Geffen School of Medicine. "We further suspect that defective regulation of GPIHBP1 will ultimately be shown to be related to acquired hyperlipidemias in humans."

Targeting the molecule could someday become a means of treating high levels of cholesterol and other fats, the researchers said.

They published the findings in the April isssue of Cell Metabolism.

According to the UCLA team, GPIHBP1 was first discovered in mice lacking certain genes. These mice had very "milky" plasma, reflecting very large amounts of triglycerides floating in the blood, explained co-researcher Dr. Stephen Young, professor of medicine and human genetics.

"We would like to understand whether the regulation of GPIHBP1 by diet is important in the overall regulation of lipolysis [fat breakdown] and in regulating plasma triglyceride levels in humans," Young said.

One key finding: the suggestion that endothelial cells, the cells that line blood vessels, might play an active role in high blood fat levels. "From the beginning, we hypothesized that GPIHBP1 would be expressed on the surface of endothelial cells," Young said. "This suspicion was borne out by our experiments."

Interestingly, the molecule was not found in the brain, whose cells mainly use sugar, rather than fats, for energy.

"These differences suggest that endothelial cells may play an active role in regulating the delivery of lipid nutrients to different tissues," Beigneux said.

Whatever the practical applications of the finding may turn out to be, the discovery is significant, Young said, because it shows that "GPIHBP1 is fundamentally important in understanding lipolysis." Lipolysis, or fat breakdown, creates the dangerous fatty substances that can block blood vessels. But it also creates the "good" HDL cholesterol particles that help protect against artery clogs, he noted.

"Until the discovery of GPIHBP1, it was unclear which molecule on the surface of endothelial cells facilitated lipolysis," he said. "We believe that GPIHBP1 is the platform for lipolysis on the surface of endothelial cells."

More information

Find out more about blood fats at the American Heart Association.

SOURCES: Stephen Young, M.D., professor, medicine and human genetics; Anne Beigneux, Ph.D., assistant investigator, University of California, Los Angeles; April 2007, Cell Metabolism

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