The role of diet and exercise in the transgenerational epigenetic landscape of T2DM
Abstract
Epigenetic changes are caused by biochemical regulators of gene expression that can be transferred across generations or through cell division. Epigenetic modifications can arise from a variety of environmental exposures including undernutrition, obesity, physical activity, stress and toxins. Transient epigenetic changes across the entire genome can influence metabolic outcomes and might or might not be heritable. These modifications direct and maintain the cell-type specific gene expression state. Transient epigenetic changes can be driven by DNA methylation and histone modification in response to environmental stressors. A detailed understanding of the epigenetic signatures of insulin resistance and the adaptive response to exercise might identify new therapeutic targets that can be further developed to improve insulin sensitivity and prevent obesity. This Review focuses on the current understanding of mechanisms by which lifestyle factors affect the epigenetic landscape in type 2 diabetes mellitus and obesity. Evidence from the past few years about the potential mechanisms by which diet and exercise affect the epigenome over several generations is discussed.
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High-fat feeding in mice induced PGC1α hypermethylation that was transferable to the offspring; maternal exercise prevented high-fat feeding hypermethylation of PGC1α and mitigated epigenetic associated metabolic dysfunction in the offspring.
“High-fat feeding in mice induced PGC1α hypermethylation that was transferable to the offspring. Maternal exercise, on the other hand, prevented high-fat feeding hypermethylation of PGC1α and mitigated epigenetic associated metabolic dysfunction in the offspring (138).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [138]
Moderate exercise during pregnancy in humans reduces the risk for obesity during the progeny's childhood and preadolescence.
“Indeed, moderate exercise during pregnancy in humans is advised because it reduces the risk for obesity during the progeny’s childhood and preadolescence (138).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [138]
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Epigenetic Programming and Fetal Metabolic Programming
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- Authors
- Barrès, R., & Zierath, J. R.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Zierath, Juleen R.
- Venue
- Nature Reviews Endocrinology
- Published
- 2016-06-17
- Volume
- 12
- Issue
- 8
- Pages
- 441-451
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2443002311
- Cited by
- 198
- References
- 113
- Citations by year
- 2026: 11 · 2025: 11 · 2024: 21 · 2023: 13 · 2022: 14 · 2021: 22 · 2020: 16 · 2019: 28 · 2018: 22 · 2017: 34 · 2016: 6
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Karolinska Institutet
- Vetenskapsrådet
- Novo Nordisk Fonden (NNF14OC0009941)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Nutrition, Genetics, and Disease
- Keywords
- type 2 diabetes, transgenerational epigenetic inheritance, diet, physical activity, epigenome, DNA methylation, histone modifications, insulin resistance, obesity, lifestyle factors, epigenetic inheritance, cell type-specific gene expression, environmental stressors
- MeSH terms
- Diabetes Mellitus, Type 2, Diet, Female, Heterozygote, Humans, Life Style, Male, Role, Exercise, DNA Methylation, Genetic Predisposition to Disease, Epigenesis, Genetic
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