The researchers also found that some long-chain fatty acids, particularly a common one called oleic acid, were especially effective for promoting cholesterol uptake. They provided evidence that oleic acid acts to drive a cholesterol transport protein from within the intestinal cell to the cell surface, where it can interact with cholesterol passing through the gut and pull it into the cell. More details of the new work will be published next week.
Their findings suggest a tightly regulated system in which cholesterol is only taken up by the intestine in the presence of fats. One reason such regulation is important, Dr. Walters said, is that unprocessed cholesterol can be toxic to cells and requires fatty acid-mediated modification to render it safe in a process called esterification.
"In nature, cholesterol and fatty acids go hand in hand. It makes sense that you could use dietary fatty acids as a cue for the transport protein to translocate to the cell surface and that dietary cholesterol may be available for absorption," he said. "The protein isn't displayed on the cell surface unless its preferred substrate for making cholesterol less toxic is also there."
Dr. Walters and his colleagues are now exploring the system's potential for studying and testing compounds that can block the absorption of dietary cholesterol, including one drug already on the market.
"Diet is a huge modulator of human disease," says Dr. Walters. "Our work demonstrates the power of the zebrafish larval system to provide fresh insights into the process of intestinal cholesterol absorption. It gives us a way to look at these processes for the first time in the context of a whole organism."
|Contact: Phyllis Edelman|
Genetics Society of America