Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations

Environmental factors such as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. Epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol (RSV) HFD + RSV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RSV groups and their offspring. Molecularly, a significant increase in DNA methylation (5-mC) levels, as well as increased gene expression of ( and in HFD + RSV F1 group, were found. Furthermore, a significant increase of N -Methyladenosine methylation (m A) levels in HFD+RSV F1, as well as changes in gene expression of its enzymes ) and were found. Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as , , the pro-inflammatory factors monocyte chemoattractant protein 1 (Mcp-1) and in HFD+RSV and HFD+RSV F1 groups. Moreover, there was increased gene expression of neurotrophins such as ), Neurotrophin-3 (Nt3), and its receptors and . Likewise, an increase in protein levels of brain-derived neurotrophic factor (BDNF) and phospho-protein kinase B (p-Akt) in HFD+RSV F1 was found. These results suggest that maternal RSV supplementation under HFD intake prevents cognitive decline in senescence-accelerated mice prone 8 (SAMP8) adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, and restoring the epigenetic landscape as well as synaptic plasticity.