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

• Published in: International journal of molecular sciences Vol. 22; no. 3; p. 1453
• Main Authors: Izquierdo, Vanesa, Palomera-Ávalos, Verónica, Pallàs, Mercè, Griñán-Ferré, Christian
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.02.2021; MDPI
• Subjects: Adenosine - analogs & derivatives; Adenosine - chemistry; Age; Aging; AKT protein; Animals; Body Weight; Brain - physiology; Brain research; Brain-derived neurotrophic factor; Cognition; Cognition & reasoning; Cognitive ability; cognitive decline; Cytokines; Deoxyribonucleic acid; Diet; Diet, High-Fat; Dietary Supplements; Dioxygenase; DNA; DNA Methylation; DNA methyltransferase; DNMT1 protein; Epigenesis, Genetic; Epigenetics; Epigenomics; Female; Gene expression; Growth factors; Health care; High fat diet; Inflammation; Interleukin 1; Interleukin 6; Ketoglutaric acid; Leptin; Leptin - blood; Male; Maternal Exposure; Maze Learning; Memory; Methylation; Mice; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; N6-methyladenosine; Neurodegeneration; Neurodegenerative Diseases; Neuronal Plasticity; Neuropathology; Nutrition research; Obesity - metabolism; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Proteins; resveratrol; Resveratrol - pharmacology; SAMP8; Senescence; Transforming growth factor-b1; Triglycerides; Triglycerides - blood; Triglycerides - metabolism; Tumor necrosis factor-TNF; 6< Methyladenosine methylation; sup> N< multigenerational inheritance; SAMP8; high-fat diet; aging; cognitive decline; resveratrol; epigenetics
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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 (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.