November 14, 2013
Genetically Engineered Tomatoes Lower Cholesterol
[ Watch the Video: GMO Tomato Mimics HDL, Lowers Cholesterol ]
Brett Smith for redOrbit.com - Your Universe Online
A long-overlooked lipid found in the small intestine has a greater role in generating high cholesterol levels and inflammation than previously thought, according to new research published in Journal of Lipid Research.
The researchers also discovered that they could lower the negative impact of these lipids in mice by giving the animals a novel, genetically-engineered tomato created to mimic HDL, or “good,” cholesterol.
"These lipids may be a new culprit that we can target in the small intestine in fighting atherosclerosis," said study author Dr. Alan Fogelman, director of the atherosclerosis research unit at the David Geffen School of Medicine at UCLA.
Doctors had believed that the small intestine responds to a high-fat, high-cholesterol diet by simply packaging the fat and cholesterol for shipment to the liver. After arriving at the liver, the fat was believed to spur higher blood levels of LDL, or "bad," cholesterol, lower levels of HDL and more dangerous systemic inflammation.
However, the authors of the new study showed that unsaturated lysophosphatidic acids (LPAs), which were overlooked because of their relatively small concentration compared to cholesterol, may play a significant role in adding to the factors that cause atherosclerosis.
In the study, scientists found that mice fed a high-fat, high-cholesterol diet showed double the amount of LPAs in the small intestine compared to mice fed a low-fat diet. When researchers added LPAs at one part per million to the low-fat, low-cholesterol mouse food, they saw the same jump in LPAs in the small intestine as seen for the high-fat diet. This addition of LPAs to the low-fat food also changed patterns of gene expression in the small intestine, as well as cholesterol levels and blood markers of inflammation in lab mice – to the point where they resembled those seen via a high-fat, high-cholesterol diet.
The findings indicate that targeting LPAs in the small intestine could stop changes in blood cholesterol and inflammation before the fat from the intestine reaches the liver, the researchers said.
"Recognizing the importance of these minor lipids in the small intestine may lead to ways to reduce their levels and prevent abnormalities in blood levels of 'good' and 'bad' cholesterol that contribute to heart attack and stroke," Fogelman said.
To see if they could reduce the effect of these lipids, the research team created genetically-engineered tomatoes that produced a small peptide called 6F that replicates the action of apoA-1, the key protein in HDL.
Freeze-dried tomato powder from the engineered plants was then added to low-fat, low-cholesterol mouse food that was also supplemented with LPAs. The same dose of the tomato powder was also added to the high-fat high- cholesterol diet.
The scientists found that the addition of just 2.2 percent of genetically engineered tomatoes prevented a rise in the level of LPAs in the small intestine, an increase in "bad" cholesterol, a decrease in "good" cholesterol and systemic inflammation.
The study team said future research will center on finding genetic signaling pathways that may be targets for treatment.
"Identifying the role of these specific lipids in the small intestine and new ways to target them will hopefully provide new insights and lead to new treatments," said study author Judith Gasson, a professor of medicine and biological chemistry at UCLA.