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 l...

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Main Authors: Vanesa Izquierdo, Verónica Palomera-Ávalos, Mercè Pallàs, Christian Griñán-Ferré
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/3/1453
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author Vanesa Izquierdo
Verónica Palomera-Ávalos
Mercè Pallàs
Christian Griñán-Ferré
author_facet Vanesa Izquierdo
Verónica Palomera-Ávalos
Mercè Pallàs
Christian Griñán-Ferré
author_sort Vanesa Izquierdo
collection DOAJ
description 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 <i>DNA methyltransferase 1</i> (<i>Dnmt1)</i> and <i>Dnmt3a</i> in HFD + RSV F1 group, were found. Furthermore, a significant increase of N<sup>6</sup>-Methyladenosine methylation (m<sup>6</sup>A) levels in HFD+RSV F1, as well as changes in gene expression of its enzymes <i>Methyltransferase like 3 (Mettl3</i>) and <i>FTO alpha-ketoglutarate dependent dioxygenase (Fto)</i> were found. Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as <i>Interleukin 1β (Il1-β), Interleukin 6 (Il-6)</i>, <i>Tumor necrosis factor-α (Tnf-α), C-X-C motif</i><i>chemokine ligand 10 (Cxcl-10)</i>, the pro-inflammatory factors monocyte chemoattractant protein 1 (Mcp-1) and <i>Tumor growth factor-β1 (Tgf-β1)</i> in HFD+RSV and HFD+RSV F1 groups. Moreover, there was increased gene expression of neurotrophins such as <i>Neural growth factor (Ngf</i>), Neurotrophin-3 (Nt3), and its receptors <i>Tropomyosin receptor kinase TrkA</i> and <i>TrkB</i>. 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.
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spelling doaj.art-5f3ac6ee680544468dc2edc8040a343c2023-12-03T11:58:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01223145310.3390/ijms22031453Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over GenerationsVanesa Izquierdo0Verónica Palomera-Ávalos1Mercè Pallàs2Christian Griñán-Ferré3Department of Pharmacology and Therapeutic Chemistry, Institut de Neurociències—Universitat de Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, SpainDepartment of Cellular and Molecular Biology, University Center of Biological and Agricultural Sciences, University of Guadalajara, km 15.5 Guadalajara-Nogales Highway, Zapopan 45110, Jalisco, MexicoDepartment of Pharmacology and Therapeutic Chemistry, Institut de Neurociències—Universitat de Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, SpainDepartment of Pharmacology and Therapeutic Chemistry, Institut de Neurociències—Universitat de Barcelona, Avda. Joan XXIII, 27, 08028 Barcelona, SpainEnvironmental 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 <i>DNA methyltransferase 1</i> (<i>Dnmt1)</i> and <i>Dnmt3a</i> in HFD + RSV F1 group, were found. Furthermore, a significant increase of N<sup>6</sup>-Methyladenosine methylation (m<sup>6</sup>A) levels in HFD+RSV F1, as well as changes in gene expression of its enzymes <i>Methyltransferase like 3 (Mettl3</i>) and <i>FTO alpha-ketoglutarate dependent dioxygenase (Fto)</i> were found. Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as <i>Interleukin 1β (Il1-β), Interleukin 6 (Il-6)</i>, <i>Tumor necrosis factor-α (Tnf-α), C-X-C motif</i><i>chemokine ligand 10 (Cxcl-10)</i>, the pro-inflammatory factors monocyte chemoattractant protein 1 (Mcp-1) and <i>Tumor growth factor-β1 (Tgf-β1)</i> in HFD+RSV and HFD+RSV F1 groups. Moreover, there was increased gene expression of neurotrophins such as <i>Neural growth factor (Ngf</i>), Neurotrophin-3 (Nt3), and its receptors <i>Tropomyosin receptor kinase TrkA</i> and <i>TrkB</i>. 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.https://www.mdpi.com/1422-0067/22/3/1453cognitive declineepigeneticsresveratrolhigh-fat dietagingSAMP8
spellingShingle Vanesa Izquierdo
Verónica Palomera-Ávalos
Mercè Pallàs
Christian Griñán-Ferré
Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations
International Journal of Molecular Sciences
cognitive decline
epigenetics
resveratrol
high-fat diet
aging
SAMP8
title Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations
title_full Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations
title_fullStr Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations
title_full_unstemmed Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations
title_short Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations under Maternal High-Fat Diet Intake: Epigenetic Inheritance over Generations
title_sort resveratrol supplementation attenuates cognitive and molecular alterations under maternal high fat diet intake epigenetic inheritance over generations
topic cognitive decline
epigenetics
resveratrol
high-fat diet
aging
SAMP8
url https://www.mdpi.com/1422-0067/22/3/1453
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