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

Weimin Guo, Dayong Wu, Maria C. Dao, Lijun Li, Erin D. Lewis, Edwin F. Ortega, Heesun Eom, Michael Thomas, Mariana Nikolova-Karakashian, Mohsen Meydani, Simin N. Meydani

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Pages (from-to)2950-2960
Number of pages11
JournalJournal of Nutrition
Issue number11
StatePublished - Nov 1 2020

Bibliographical note

Publisher Copyright:
Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.


  • Ceramide
  • Fruits and vegetables
  • Gut microbiota
  • Hepatic steatosis
  • Inflammation
  • Nonalcoholic fatty liver disease

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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