Zebrafish research shows how dietary fat regulates cholesterol absorption

June 22, 2012

Buttery shrimp. Fried eggs. Burgers and fries. New research suggests there may be a biological reason why fatty and cholesterol-rich foods are so appealing together.

It has been known for more than 40 years that dietary fat promotes cholesterol uptake, but fundamental aspects of that process remain poorly understood. James Walters, Ph.D., and his colleagues at the Carnegie Institution for Science are using zebrafish to better understand the of cholesterol processing and have discovered a surprising link between and cholesterol absorption.

"One reason these questions remain unknown is because of the difficulty of studying such a complex biological system as the intestine," which in addition to multiple cell types also includes a diverse array of enzymes, mucus, and , he said in a June 20 presentation at the ongoing 2012 International Zebrafish Development and Genetics Conference in Madison, Wisconsin.

As a postdoctoral fellow in Dr. Steven Farber's lab at the Carnegie Institution for Science, in Baltimore, Maryland, Dr. Walters turned to young zebrafish, which provide a biologically complete and scientifically accessible system for studying the workings of the gut.

"Because the larval zebrafish are optically clear, we can visualize fat transport and processing by looking right through their body wall into the intestine where the action is," Dr. Walters said.

He developed a way to feed zebrafish a diet high in lipids (e.g., fat and cholesterol) or high in protein and low in lipids. He accomplished this by turning to the chicken egg, whipping fish water with the yolk for a high-lipid diet and the egg white as a high-protein diet. Before feeding these diets, fluorescently tagged cholesterol or fatty acid was added, enabling the microscopic viewing of how lipids are absorbed and processed by the .

Dr. Walters found that cholesterol was only absorbed when the fish ate a high-fat diet, not a low-fat diet. The fats and cholesterol were packaged into separate and clearly visible compartments within the cells. "You can tell which larvae had eggs for breakfast," he said.

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 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 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 absorption. It gives us a way to look at these processes for the first time in the context of a whole organism."

Explore further: Intake of the right fatty acids can help to prevent heart attacks

Related Stories

Intake of the right fatty acids can help to prevent heart attacks

June 30, 2011
There is much confusion at present about the importance of fatty acids in preventing heart attacks. Recent studies have questioned the need to reduce the intake of saturated fatty acids in the diet and to increase that of ...

Recommended for you

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

Omega-3 fatty acids fight inflammation via cannabinoids

July 18, 2017
Chemical compounds called cannabinoids are found in marijuana and also are produced naturally in the body from omega-3 fatty acids. A well-known cannabinoid in marijuana, tetrahydrocannabinol, is responsible for some of its ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.