Love apples could help heal hearts

Tomato could soon be living up to its ‘love apple’ title, improving heart health by lowering cholesterol. UCLA researchers have genetically engineered tomatoes to produce a peptide that mimics the actions of good cholesterol when consumed.

Published in the April issue of the Journal of Lipid Research, the study found that mice fed these tomatoes had less inflammation and plaque build-up in their arteries.

“This is one of the first examples of a peptide that acts like the main protein in good cholesterol and can be delivered by simply eating the plant,” said senior author Dr Alan M Fogelman, executive chair of the department of medicine and director of the atherosclerosis research unit at the David Geffen School of Medicine at UCLA. “There was no need to isolate or purify the peptide - it was fully active after the plant was eaten.”

The researchers found that the peptide was active in the small intestine after eating, but not in the blood. They say this suggests that targeting the small intestine may be a new strategy to prevent diet-induced atherosclerosis.

The tomatoes were genetically engineered to produce 6F, a small peptide that mimics the action of apoA-1, the chief protein in high-density lipoprotein (HDL), also known as ‘good’ cholesterol. The tomatoes were fed to mice who lacked the ability to remove low-density lipoprotein (LDL) - ‘bad’ cholesterol - from their blood and readily developed inflammation and atherosclerosis when consuming a high-fat diet.

The researchers found that mice that ate the peptide-enhanced tomatoes, which accounted for 2.2% of their Western-style, high-fat diet, had significantly lower levels of inflammation; higher paraoxonase activity, an antioxidant enzyme associated with good cholesterol; higher levels of good cholesterol; decreased lysophosphatidic acid, a tumour promoter that accelerates plaque build-up in the arteries in animal models; and less atherosclerotic plaque.

Several hours after the mice finished eating, the intact peptide was found in the small intestine, but no intact peptide was found in the blood. According to researchers, this strongly suggests that the peptide acted in the small intestine and was then degraded to natural amino acids before being absorbed into the blood, as is the case with the other peptides and proteins in the tomato.

“It seems likely that the mechanism of action of the peptide-enhanced tomatoes involves altering lipid metabolism in the intestine, which positively impacts cholesterol,” said the study's corresponding author, Srinavasa T Reddy, a UCLA professor of medicine and of molecular and medical pharmacology.

Fogelman says that if the work is shown to apply to humans, consuming forms of genetically modified foods that contain apoA-1-related peptides could potentially help improve these conditions.

The peptide would be considered a drug if given by injection or in a purified pill form, but when it is part of the fruit of a plant, it may be no different from a safety standpoint than the food in which it is contained - and may even be better tolerated than a drug, Fogelman said. The peptide has the potential to be developed into a nutritional supplement.

“This is one of the first examples in translational research using an edible plant as a delivery vehicle for a new approach to cholesterol,” said Judith Gasson, a professor of medicine and biological chemistry, director of UCLA’s Jonsson Comprehensive Cancer Center and senior associate dean for research at the Geffen School of Medicine. “We will be closely watching this novel research to see if these early studies lead to human trials.”