Department of Pharmacology and Therapeutic Chemistry, Institut de Neurociències-Universitat de Barcelona, Avda. Joan XXIII, 27., 08028 Barcelona, Spain.
Department of Cellular and Molecular Biology, University Center of Biological and Agricultural Sciences, University of Guadalajara, km 15.5 Guadalajara-Nogales Highway, Zapopan 45110, Jalisco, Mexico.
Int J Mol Sci. 2021 Feb 1;22(3):1453. doi: 10.3390/ijms22031453.
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 (mA) 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.
环境因素，如母体高脂肪饮食（HFD）摄入，会增加成年后代与年龄相关的认知能力下降的风险。表观遗传机制是饮食效应与跨代神经退行性变之间的可能联系。在这里，我们发现高脂肪饮食中添加白藜芦醇（RSV）的 HFD+RSV 组及其后代的甘油三酯水平显著降低。首先，我们在 HFD+RSV 组及其后代中获得了更好的认知表现。从分子水平上看，HFD+RSV F1 组的 DNA 甲基化（5-mC）水平显著升高，以及 和 的基因表达增加。此外，我们发现 HFD+RSV F1 的 N6-甲基腺苷（mA）水平显著升高，以及其酶的基因表达发生变化 和 。此外，我们发现促炎标志物如 、 、促炎因子单核细胞趋化蛋白 1（Mcp-1）和 在 HFD+RSV 和 HFD+RSV F1 组中的基因表达水平降低。此外，神经生长因子如 、神经生长因子-3（Nt3）及其受体 和 的基因表达增加。同样，我们发现 HFD+RSV F1 中的脑源性神经营养因子（BDNF）和磷酸化蛋白激酶 B（p-Akt）蛋白水平升高。这些结果表明，HFD 摄入下母体 RSV 补充可预防快速老化小鼠 8 号（SAMP8）成年后代的认知能力下降，促进甘油三酯和瘦素血浆水平降低、促炎谱改变以及表观遗传景观和突触可塑性的恢复。
