Dietary fruit and vegetable supplementation suppresses diet-induced atherosclerosis in LDL receptor knockout mice

Authors: GUO, WEIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; KIM, SHARON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LI, LIJUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORTEGA, EDWIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; THOMAS, MICHAEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, MOHSEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/24/2020
Publication Date: 2/9/2021
Citation: Guo, W., Kim, S.H., Wu, D., Li, L., Ortega, E.F., Thomas, M., Meydani, S.N., Meydani, M. 2021. Dietary fruit and vegetable supplementation suppresses diet-induced atherosclerosis in LDL receptor knockout mice. Journal of Nutrition. 151(4):902-910. https://doi.org/10.1093/jn/nxaa410.
DOI: https://doi.org/10.1093/jn/nxaa410

Interpretive Summary: Observational studies suggest that eating a lot of fruits and vegetables (F&V) is associated with reduced risk for cardiovascular diseases. However, direct evidence to support these recommendations is not available. Scientists at the JM USDA Human Nutrition Research Center at Tufts University in Boston, Massachusetts, investigated whether eating a lot of various types of F&V will prevent atherosclerosis (plaques formed in the arteries "clogged arteries", and a leading cause of cardiovascular disease onset). Our results demonstrated that eating equivalent to 8-9 servings of F&V reduced diet-induced atherosclerosis by 90%. This effect of F&V was associated with reduced inflammation, improved blood lipid profile, and increased healthy gut microbiota. Our data suggest that increasing consumption of F&V will reduce the risk for atherosclerosis.

Technical Abstract: Background. Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. Objectives. We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. Methods. Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-alpha concentrations, gut microbiota, and liver TNF-alpha and fatty acid synthase (Fasn) mRNA concentrations were assessed. Results. F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P < 0.001) independent of impact on weight, whereas no difference was found between Ath + FV and CON groups in these 2 pathologic markers. Furthermore, F&V supplementation prevented Ath diet-induced dyslipidemia (high concentrations of serum TG and VLDL cholesterol and lower concentrations of HDL cholesterol), reduced serum TNF-alpha concentration (by 21.5%), suppressed mRNA expression of liver TNF-alpha and Fasn, and ameliorated Ath-induced gut microbiota dysbiosis. Conclusions. Our results indicate that consuming a large quantity and variety of F&Vs causally attenuates diet-induced atherosclerosis and hepatic steatosis in mice. These effects of F&Vs are associated with, and may be mediated through, improved atherogenic dyslipidemia, alleviated gut dysbiosis, and suppressed inflammation.