New Discovery Offers Hope For Controlling Cholesterol, Atherosclerosis

December 22, 1998

Offers Hope for Controlling Obesity, Atherosclerosis

Scientists have found a protein in the small intestine that may force medical science to re-think long-held beliefs about how the human body absorbs cholesterol and fat, according to a report in the journal Biochemistry. It had been assumed that such lipids simply diffused from the small intestine into the blood stream, a process that is very difficult to control. Researchers say the newly discovered protein is directly involved in facilitating uptake of dietary lipids and offers a better target for drugs to combat obesity and heart disease.

The finding is detailed in both the web and Dec. 22 print editions of the peer-reviewed journal Biochemistry, published by the American Chemical Society, the world's largest scientific society.

The small intestine is the human body's main entrance for dietary cholesterol and fat. A 1990 Biochemistry paper by some of the current authors suggested a protein might be directly involved in the transport, but none have been found until now. "The identification of such a protein opens the very real possibility that we can inhibit the activity of the protein and thereby significantly reduce the level of cholesterol in the blood," claims biochemist Michael Phillips, Ph.D. of MCP Hahnemann University in Philadelphia.

Though the researchers admit they don't yet know exactly how the newly found protein works, lead author Helmut Hauser, Ph.D. of the Swiss Federal Institute of Technology in Zurich compares it to a bus stop on the road leading through the gastrointestinal system. He says that cholesterol and fat molecules ride on bile salt "buses" and "when one comes to (the transport) protein, it's like the bus driving to the bus stop. While they stop, the passengers get out of the bus and into your body." Hauser adds that an inhibitor drug could be made to fit perfectly in those "parking spaces" so that "the buses cannot park because the lot is already occupied, and they travel on until it's too late to participate in absorption and the fat ends up in the feces."

The scientists think their discovery can help reduce and treat obesity as well as artherosclerosis, which can lead to heart disease, the western world's number one killer.

The authors say they have already found and patented inhibitory compounds that, in principle, show how to solve these problems, even as the research continues to evolve. "The receptor is well accessible to an orally administered drug," says co-author Georg Schulthess, M.D. at the University of Zurich, "preliminary studies show that the activity of the receptor can be inhibited completely using some synthesized peptides."

Researchers say that several more years of intensive research are needed before any product, food additive or drug is available.
A nonprofit organization with a membership of more than 155,000 chemists and chemical engineers, the American Chemical Society publishes scientific journals and databases, convenes major research conferences, and provides educational, science policy and career programs in chemistry. Its main offices are in Washington, D.C., and Columbus, Ohio.

American Chemical Society

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