Effect of Dietary Grapes on Female C57BL6/J Mice Consuming a High-Fat Diet: Behavioral and Genetic Changes

Abstract

(1) Background: Adverse effects of a chronic high-fat diet (HFD) on murine behavior, cognition, and memory are well established. Polyphenols such as resveratrol, anthocyanins, and flavonoids, that are known for antioxidative and anti-inflammatory properties, are present in grapes. The objective of this work was to determine if the dietary intake of grapes has the potential of alleviating HFD-induced deficiencies. (2) Methods: The effect of dietary grape intake was studied using behavioral assays and high throughput genome-wide RNA transcriptome analyses with female C57BL6/J mice. (3) Results: Mice that were fed a HFD from 3-weeks of age showed anxiety-like behaviors compared with the standard diet (STD). This HFD-induced effect was attenuated by supplementing the HFD with 1% grape powder (HF1G) (open field test). Similar results were observed with the novel object recognition test; there was a significant difference in time spent exploring a novel object between the HFD and the HF1G groups. There was no significant difference between the HFD1G and the STD groups. Based on the RNA-Seq analysis, genetic expression in the brain varied as a result of diet, with 210, 360, and 221 uniquely expressed genes in the STD, HFD, and HF1G groups, respectively. Cluster analysis revealed that the HFIG group mapped more closely with the STD group than the HFD group. Focusing on some specific areas, based on genetic expression, Dopamine receptor 2 (Drd2) was increased in the HFD group and normalized in the HF1G group, relative to the STD group. In addition, as judged by cluster hierarchy, the expression of genes that are associated with the dopamine receptor 2 pathway were increased in the HFD group, whereas the pattern that was derived from mouse brain from the HF1G group showed greater similarity to the STD group. KEGG pathway analyses were consistent with these results. For example, neuroactive ligand-receptor interaction (KEGG ID: mmu04080) was altered due to HFD compared with STD, but normalized by grape supplementation or the HFD; there was no significant difference between the STD and HF1G groups. In addition, the expression of genes related to feeding behavior, such as Adora2a, Th, and Trh, were also increased in the HFD group compared with the STD group, and attenuated by grape supplementation. (4) Conclusions: Dietary grape consumption has positive effects on behavior and cognition that are impaired by a HFD. Attenuation of these effects correlates with global transcriptional changes in mouse brain.