Dietary fruits and vegetables mitigate cognitive impairment in mice with high-fat diet-induced obesity: A pilot study

Authors: GUO, WEIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Shukitt Hale, Barbara; 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; MEYDANI, SIMIN NIKBIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Nutritional Neuroscience
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2025
Publication Date: 10/22/2025
Citation: Guo, W., Shukitt Hale, B., Wu, D., Li, L., Meydani, S. 2025. Dietary fruits and vegetables mitigate cognitive impairment in mice with high-fat diet-induced obesity: A pilot study. Nutritional Neuroscience. 29(4):466-475. https://doi.org/10.1080/1028415X.2025.2572546.
DOI: https://doi.org/10.1080/1028415X.2025.2572546

Interpretive Summary: Obesity is associated with an increased risk of cognitive decline. There is some evidence that a higher intake of fruits and vegetables may be associated with a lower risk of cognitive impairment. This study examined whether eating fruits and vegetables could prevent cognitive decline in mice with high-fat diet-induced obesity. Young, male mice were randomly assigned to one of five diet groups: low fat, or high fat diet supplemented with 0%, 5%, 10%, or 15% of a mixture of commonly consumed fruits and vegetables. These levels correspond to approximately 0, 3, 5-7, or 8-9 servings of fruits and vegetables per day for humans, respectively. A test to measure memory was performed after mice consumed the diets for 17 weeks. Mice fed the high fat diet showed greater cognitive impairment compared to the low fat group. However, eating fruits and vegetables along with the high fat diet improved memory in a dose-dependent manner, with higher intake providing more protection. The results suggest that fruit and vegetable intake can prevent cognition impairment caused by a high-fat diet. Additional research is required to better understand the reasons behind this protection.

Technical Abstract: Objectives: The rising prevalence of cognitive decline linked to obesity is becoming a significant public health issue. Epidemiological studies indicate that a higher intake of fruits and vegetables (F&V) may be associated with a lower risk of cognitive impairment, although the evidence for the causal relationship is lacking. This study examined whether F&V supplementation could prevent cognitive decline in mice with high-fat diet-induced obesity. Methods: Male C57BL/6J mice (6 weeks old) were randomly assigned to one of five diet groups (12 mice per group): low fat (LF, 10% kcal fat) diet, or high fat (HF0, 45% kcal fat) diet supplemented with 0% (HF0), 5% (HF5), 10% (HF10), or 15% (HF15) of a mixture of F&V (wt/wt). These levels of supplementation correspond to approximately 0, 3, 5-7, or 8–9 servings of F&V per day for humans, respectively. The novel object recognition test was performed after mice consumed the respective diets for 17 weeks. Results: Mice fed the Western-style HF diet spent less time exploring the novel object, indicating significant cognitive impairment compared to the LF group. Conversely, F&V supplementation alleviated the HF diet-induced cognitive deficits in a dose-dependent manner. Discussion: The results from this pilot study suggest the causal link between F&V intake and the prevention of cognition impairment caused by a Western-style high-fat diet, establishing a foundation for further investigation into the protective effects of F&V consumption on obesity-related cognitive decline. Additional research is required to better understand the underlying mechanisms.