Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations Under Maternal High-Fat Diet Intake: Multigenerational Epigenetic Inheritance.

Version 1 : Received: 4 December 2020 / Approved: 4 December 2020 / Online: 4 December 2020 (14:54:58 CET)

A peer-reviewed article of this Preprint also exists.

Izquierdo, V.; Palomera-Ávalos, V.; Pallàs, M.; Griñán-Ferré, C. Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations Under Maternal High-Fat Diet Intake: Epigenetic Inheritance Over Generations. Int. J. Mol. Sci. 2021, 22, 1453. Izquierdo, V.; Palomera-Ávalos, V.; Pallàs, M.; Griñán-Ferré, C. Resveratrol Supplementation Attenuates Cognitive and Molecular Alterations Under Maternal High-Fat Diet Intake: Epigenetic Inheritance Over Generations. Int. J. Mol. Sci. 2021, 22, 1453.

Abstract

Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The 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 HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.

Keywords

cognitive decline; epigenetics; HFD; aging; SAM0P8; m6A, multigenerational inheritance.

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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