Zebrafish research shows how dietary fat regulates cholesterol absorption
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 cellular mechanisms of cholesterol processing and have discovered a surprising link between dietary fat 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 symbiotic bacteria, 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 intestinal cells.
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 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."
Provided by Genetics Society of America
- How drug that blocks cholesterol absorption from the diet works Jun 03, 2008 | not rated yet | 0
- Transparent zebrafish a must-see model for atherosclerosis Mar 05, 2009 | not rated yet | 0
- Columbia research shows novel benefits of fatty acids in arteries Feb 05, 2009 | not rated yet | 0
- Intake of the right fatty acids can help to prevent heart attacks Jun 30, 2011 | not rated yet | 0
- Lowering your cholesterol may decrease your risk of cancer Feb 23, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
By discovering the new mechanism by which estrogen suppresses lipid synthesis in the liver, UC Irvine endocrinologists have revealed a potential new approach toward treating certain liver diseases.
Medical research May 23, 2013 | not rated yet | 0 |
Aortic arch pulse wave velocity, a measure of arterial stiffness, is a strong independent predictor of disease of the vessels that supply blood to the brain, according to a new study published in the June issue the journal ...
Medical research May 23, 2013 | not rated yet | 0
Since the discovery of Prontosil in 1932, sulfonamide antibiotics have been used to combat a wide spectrum of bacterial infections, from acne to chlamydia and pneumonia. However, their side effects can include serious neurological ...
Medical research May 23, 2013 | not rated yet | 0 |
Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as ...
Medical research May 23, 2013 | 5 / 5 (3) | 0 |
Spanish researchers have discovered that the daily clearance of neutrophils from the body stimulates the release of hematopoietic stem cells from the bone marrow into the bloodstream, according to a report published today ...
Medical research May 23, 2013 | 5 / 5 (2) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
4 hours ago | 5 / 5 (1) | 0 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
9 hours ago | 5 / 5 (3) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
3 hours ago | not rated yet | 0
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
6 hours ago | 5 / 5 (1) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
7 hours ago | 5 / 5 (2) | 0 |
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
4 hours ago | not rated yet | 0