A novel combination of fruits and vegetables prevents diet-induced hepatic steatosis and metabolic dysfunction in mice

Authors: GUO, WEIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DAO, MARIA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LI, LIJUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LEWIS, ERIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; ORTEGA, EDWIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; EORN, HEESUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; THOMAS, MICHAEL - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; NIKOLOVA-KARAKASHIAN, MARIANA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, MOHSEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/4/2020
Publication Date: 9/16/2020
Citation: Guo, W., Wu, D., Dao, M.C., Li, L., Lewis, E., Ortega, E.F., Eorn, H., Thomas, M., Nikolova-Karakashian, M., Meydani, M., Meydani, S.N. 2020. A novel combination of fruits and vegetables prevents diet-induced hepatic steatosis and metabolic dysfunction in mice. Journal of Nutrition. 150(11):2950-2960. https://doi.org/10.1093/jn/nxaa259.
DOI: https://doi.org/10.1093/jn/nxaa259

Interpretive Summary: Observational studies show that eating more fruits and vegetables (F&V) is associated with lower prevalence of obesity and risk of liver cancer. However, evidence to support this by actually feeding different levels of F&V and documenting the effect is scarce. This information is needed in order to enable health professionals and organizations to provide the public with specific and accurate recommendations regarding F&V. Scientists at the JM USDA Human Nutrition Research Center at Tufts University in Boston, formulated an original F&V powder mix containing 24 kinds of the most commonly consumed F&V and incorporated this mix, at different levels (equivalent to 1-9 servings per day in humans), into diets of mice fed a high or low fat diet. We found that a relatively large amount (equivalent to 8 - 9 servings per day in humans) of F&V supplementation reduced inflammation, increased healthy gut microbiome, and almost totally prevented accumulation of fat in the liver, a risk factor for liver cancer, in obese mice. Several of these effects were also observed in lean mice and were not dependent on body weight reduction. Our results represent the first evidence that increased F&V consumption, as recommended by health organizations, reduces risk for liver cancer through decreasing inflammation and enhancing healthy gut microbiota. These findings will help health professionals and organizations make more specific recommendations regarding F&V consumption and reduction of risk for obesity and liver cancer.

Technical Abstract: Background: Epidemiological studies suggest that higher fruits and vegetables (F&V) consumption correlates with reduced risk of hepatic steatosis, yet evidence for causality and the underlying mechanisms is lacking. Objectives: We aimed to determine the causal relation between F&V consumption and improved metabolic disorders in mice fed high-fat (HF) (Experiment-1) or normal-fat (Experiment-2) diets and its underlying mechanisms. Methods: Six-week-old male C57BL/6J mice were randomly grouped and fed diets supplemented at 0%-15% (wt:wt) with a freeze-dried powder composed of 24 commonly consumed F&V (human equivalent of 0-9 servings/d) for 20 wk. In Experiment-1,mice were fed an HF (45% kcal fat) diet with 0% (HF0), 5%, 10%, or 15%(HF15) F&V or a matched low-fat control diet (10% kcal fat). In Experiment-2, mice were fed an AIN-93 diet (basal) (B, 16% kcal fat) with 0% (B0), 5%, 10%, or 15% (B15) F&V supplementation. Body weight and composition, food intake, hepatic steatosis, inflammation, ceramide levels, sphingomyelinase activity, and gut microbiota were assessed. Results: In Experiment-1, mice fed the HF15 diet had lower weight gain (17.9%), hepatic steatosis (48.4%), adipose tissue inflammation, blood (24.6%) and liver (33.9%) ceramide concentrations, and sphingomyelinase activity (38.8%) than HF0 mice (P < 0.05 for all). In Experiment-2, mice fed the B15 diet had no significant changes in weight gain but showed less hepatic steatosis (28.5%), blood and adipose tissue inflammation, and lower blood (30.0%) ceramide concentrations than B0 mice (P < 0.05 for all). These F&V effects were associated with favorable microbiota changes. Conclusions: These findings represent the first evidence for a causal role of high F&V intake in mitigating hepatic steatosis in mice. These beneficial effects may be mediated through changes in ceramide and/or gut microbiota, and suggest that higher than currently recommended servings of F&V may be needed to achieve maximum health benefits.