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      Genes and Diet in the Prevention of Chronic Diseases in Future Generations

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          Abstract

          Nutrition is a modifiable key factor that is able to interact with both the genome and epigenome to influence human health and fertility. In particular, specific genetic variants can influence the response to dietary components and nutrient requirements, and conversely, the diet itself is able to modulate gene expression. In this context and the era of precision medicine, nutrigenetic and nutrigenomic studies offer significant opportunities to improve the prevention of metabolic disturbances, such as Type 2 diabetes, gestational diabetes, hypertension, and cardiovascular diseases, even with transgenerational effects. The present review takes into account the interactions between diet, genes and human health, and provides an overview of the role of nutrigenetics, nutrigenomics and epigenetics in the prevention of non-communicable diseases. Moreover, we focus our attention on the mechanism of intergenerational or transgenerational transmission of the susceptibility to metabolic disturbances, and underline that the reversibility of epigenetic modifications through dietary intervention could counteract perturbations induced by lifestyle and environmental factors.

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          Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

          Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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            Nongenetic Inheritance and Its Evolutionary Implications

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              High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

              Objectives Chronic and high consumption of fat constitutes an environmental stress that leads to metabolic diseases. We hypothesized that high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa and metabolism of the offspring. Methods F0-male rats fed either HFD or chow diet for 12 weeks were mated with chow-fed dams to generate F1 and F2 offspring. Motile spermatozoa were isolated from F0 and F1 breeders to determine DNA methylation and small non-coding RNA (sncRNA) expression pattern by deep sequencing. Results Newborn offspring of HFD-fed fathers had reduced body weight and pancreatic beta-cell mass. Adult female, but not male, offspring of HFD-fed fathers were glucose intolerant and resistant to HFD-induced weight gain. This phenotype was perpetuated in the F2 progeny, indicating transgenerational epigenetic inheritance. The epigenome of spermatozoa from HFD-fed F0 and their F1 male offspring showed common DNA methylation and small non-coding RNA expression signatures. Altered expression of sperm miRNA let-7c was passed down to metabolic tissues of the offspring, inducing a transcriptomic shift of the let-7c predicted targets. Conclusion Our results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                10 April 2020
                April 2020
                : 21
                : 7
                : 2633
                Affiliations
                [1 ]Department of Medicine and Aging, School of Medicine and Health Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
                [2 ]Center for Advanced Studies and Technology (CAST), ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
                [3 ]DISC-Diversified Integrated Sport Clinic, Dubai 00000, UAE
                [4 ]Department of Psychological, Health and Territorial Sciences, School of Medicine and Health Sciences, ‘G. d’Annunzio’ University of Chieti-Pescara, 66100 Chieti, Italy
                Author notes
                Author information
                https://orcid.org/0000-0003-1756-661X
                Article
                ijms-21-02633
                10.3390/ijms21072633
                7178197
                32290086
                cd90d49b-cc38-4197-8212-e84eec28d148
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 March 2020
                : 08 April 2020
                Categories
                Review

                Molecular biology
                nutrigenetics,nutrigenomics,epigenetics,gene-nutrient interaction,transgenerational effect,non-communicable diseases

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