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Engineered Tomato Helps Cut Contributor to Clogged Arteries

Tomato slices (Agricultural Research Service/USDA)

(Agricultural Research Service/USDA)

Researchers at University of California in Los Angeles found feeding a bio-engineered tomato to lab animals cuts their production of a fatty acid believed to contribute to high cholesterol levels. The team led by Alan Fogelman, director of the atherosclerosis research unit at UCLA’s medical school published their findings in the December issue of the Journal of Lipid Research (paid subscription required).

Fogelman, with co-authors Mohamad Navab and Srinivasa Reddy, are principals in the biotechnology company Bruin Pharma that licensed the technology developed in this research from UCLA, which owns the patents.

Fogelman’s team, which includes colleagues from University of Alabama–Birmingham and University of Kentucky, investigated the role of a lipid — fat or oil — known as  unsaturated lysophosphatidic acids or LPAs found in the small intestine. The small intestine produces small amounts of LPAs, which were once considered a minor factor in the production of LDL (bad) cholesterol in the blood.

The researchers found, however, that a high-fat, high-cholesterol diet fed to lab mice caused their levels of LPAs to spike with a two-old increase. Adding LPAs to a low-fat, low-cholesterol diet resulted in much the same increase in LPAs as putting the mice as a high-fat diet. Mice that were fed LPAs with a low-fat diet experienced changes in gene expression patterns leading to increases in LDL and decreases in HDL (good) cholesterol, along with increases in blood biomarkers seen in the mice fed a high-fat, high-cholesterol diet.

The evidence, say the researchers, points to LPAs in the small intestine playing a more important role in determining LDL and HDL cholesterol levels than previously considered.  “Recognizing the importance of these minor lipids in the small intestine,” says Fogelman, “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.”

The type of bioengineered tomatoes developed at UCLA and tested in the study contains a peptide known as 6F, which acts the same way as the protein apoA-1, a key ingredient in HDL cholesterol. The UCLA team added to the diets of the test mice a freeze-dried powder made from the engineered tomatoes equivalent to 2.2 percent of the low-fat diet, supplement with LPAs. The researchers also added an equivalent amount of the enhanced tomato powder to the mice’s high-fat diet.

The results show adding the powder from the peptide-enhanced tomatoes prevented an increase in LPA levels from occuring in the small intestines of the mice fed the LPA-added low-fat diet and the mice on a high-fat diet. Mice fed ordinary (non-engineered) tomatoes showed no difference in LPA levels.

The researchers say they next want to better understand the processes that are affected by LPAs in the small intestine. That work will involve identifying the small intestine genes altered by LPAs to uncover the signaling pathways that can serve as treatment targets.

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