A specific type of lipid in the small intestine may play a greater role than previously thought in generating the high cholesterol levels and inflammation, they said.

The negative effects of these lipids in mice could be reduced by feeding the animals a new genetically engineered tomato being developed that is designed to mimic HDL ("good")

The study at University of California, Los Angeles (UCLA) focused on a group of lipids found in the small intestine called unsaturated lysophosphatidic acids (LPAs).

"These lipids may be a new culprit that we can target in the small intestine in fighting atherosclerosis," said senior author Dr Alan Fogelman.

Researchers found that LPAs, previously considered very minor because they are found in far smaller amounts in the small intestine than other lipids, may play a more direct role in contributing to the factors that cause atherosclerosis.

Scientists found that mice fed a high-fat, high-cholesterol diet showed a two-fold increase in the amount of LPAs in the small intestine over mice fed normal low-fat mouse chow.

When researchers added LPAs at only one part per million (by weight) to the normal low-fat, low-cholesterol mouse chow, they observed the same increase in LPAs in the small intestine as when the mice were fed the high-cholesterol, high-fat diet.

Surprisingly, with the addition of LPAs to the low-fat diet, the team also found alterations in the patterns of gene expression in the small intestine, changes in cholesterol levels (increases in LDL and decreases in HDL) and increases in blood markers of inflammation typically seen when the mice consumed a high-fat, high-cholesterol diet.

The findings suggest that some of the factors leading to atherosclerosis occur in the small intestine and not just the liver. The tomatoes, created at UCLA, produce a small peptide called 6F that mimics the action of apoA-1, the chief protein in HDL.

Researchers added 2.2 per cent of freeze-dried tomato powder from the peptide-enhanced tomatoes to low-fat, low-cholesterol mouse chow that was supplemented with LPAs.

They also added the same dose of the peptide-enhanced tomatoes to the high-fat high- cholesterol diet. They found that this addition to both diets prevented an increase in the level of LPAs in the small intestine and also stopped increases in "bad" cholesterol, decreases in "good" cholesterol and systemic inflammation.

Tomatoes that did not contain the peptide had no effect. The study was published in the Journal of Lipid Research.


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