Long-Term Supplementation with Fruits and Vegetables Prevents Cognitive Impairment Induced by a Western-Style High-Fat Diet in Male Mice.

BACKGROUND

Aging, obesity, and high-fat Western diets are linked to increased risk of cognitive decline. Although higher fruit and vegetable (FVs) intake may protect against cognitive decline, evidence remains inconsistent.

OBJECTIVES

This study examined whether long-term FV supplementation preserves cognitive function and modulates serum sphingolipid metabolism in mice fed low-fat or high-fat diets.

METHODS

In this long-term in vivo mouse study, male C57BL/6J mice were randomly assigned to low-fat control (LF-C), high-fat control (HF-C), or each diet supplemented with 15% FV (LF-FV, HF-FV) (n = 20/group). After 18 mo on the diets, cognitive function was assessed using the novel object recognition (NOR) test, and recognition index (RI) and discrimination index (DI) were calculated. At 21 mo, all mice were killed, and serum was collected for lipidomic analysis. Group comparisons were performed using analyses of variance with post hoc tests and correlation analyses between lipids and cognitive measures.

RESULTS

LF-C, LF-FV, and HF-FV mice showed significant increases in RI during testing (18.7%, 23.6%, and 22.2%, respectively), whereas HF-C exhibited no improvement. HF-C also had markedly reduced DI (-0.0456) relative to all other groups (0.2100-0.2323), consistent with cognitive impairment. In contrast, HF-FV mice demonstrated preserved DI and RI values comparable with those of LF controls, indicating that FV supplementation prevented high-fat diet-induced deficits. Serum lipidomic analysis revealed that HF-C mice displayed elevated total sphingomyelins (SMs) and several long-chain SM species; these elevations were largely normalized in HF-FV mice. Across all mice, higher SM amounts were consistently associated with poorer NOR performance, suggesting that changes in SMs may contribute to cognitive differences.

CONCLUSIONS

In aged male C57BL/6J mice, long-term FV supplementation mitigates cognitive decline caused by a high-fat diet. Changes in serum SM species were associated with cognitive outcomes and may be related to the protective effect of FV supplementation.