(P26-021-25) Novel High Steroidal Alkaloid Tomato Reduces the Incidence of Atherosclerotic Plaques in Apoe-/-/Ldlr-/- Double Knockout Mice Fed a High Fat/Cholesterol Diet

Objectives: Tomato steroidal alkaloids (tSAs) are a promising class of plant bioactive compounds that have putative cardioprotective benefits. Using conventional breeding, we have developed a tomato with 40x higher tSA content than typical, while otherwise nearly isogenic. This pre-liminary study aims to assess the effect of a diet containing standard tomatoes or with those high in tSAs on the development of atherosclerosis in mice pre-disposed to disease.

Methods: Apoe^-/-/Ldlr^-/- double knockout mice were randomly assigned to one of three diets: high fat and cholesterol control (HFHC: 45% kcal fat, 1.25% by weight cholesterol, n = 6), HFHC supplemented with 10% of a typical processing-type tomato (0.1 mg alkaloids/100g diet, n = 5) or 10% hybrid high alkaloid tomato (4 mg/100g diet, n = 4). Mice were fed the diets for 12 weeks, blood serum was collected for cholesterol analysis via commercially available kits, and aortas were harvested and stained en face with Oil Red O for plaque analysis. A linear model was used to compare means between control HFHC to each of the tomato groups (significance P < 0.05).

Results: Mice fed the high alkaloid tomato experienced significantly less aortic plaque (44.3% ± 4.4%) than control (60.8% ± 8.8%, P = 0.02), while mice on the standard processing tomato trended towards having less plaque (49.2% ± 12.9%, P = 0.07). Mice fed the high alkaloid tomato also had significantly lower levels of serum LDL cholesterol (198 ± 111 mg/dL) than control (332 ± 73 mg/dL, P = 0.03), while mice on the standard processing tomato had lower levels but were not significantly different (280 ± 82 mg/dL, P = 0.34).

Conclusions: Mice predisposed to heart disease consuming tomatoes for 12 weeks develop less atherosclerotic plaques than those on HFHC control, with diets containing tomatoes high in tSAs providing an even greater benefit. Further work should be done to confirm this finding in larger studies, with molecular interrogation to explore the genetic and metabolic underpinnings of this anti-atherogenic effect.

Funding Sources: Research was funded by the CFAES Office for Research & Graduate Education Internal Grants Program; Foods for Health, a focus area of the Discovery Themes at The Ohio State University; and the Dan Wampler Endowed Fellowship for Foods and Health Research.