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de Castro Barbosa T, Ingerslev LR, Alm PS, et al. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. Mol Metab. 2015;5(3):184-197doi: 10.1016/j.molmet.2015.12.002.
de Castro Barbosa, T., Ingerslev, L. R., Alm, P. S., Versteyhe, S., Massart, J., Rasmussen, M., Donkin, I., Sjögren, R., Mudry, J. M., Vetterli, L., Gupta, S., Krook, A., Zierath, J. R., & Barrès, R. (2016). High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. Molecular metabolism, 5(3), 184-197. https://doi.org/10.1016/j.molmet.2015.12.002
de Castro Barbosa, Thais, et al. "High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring." Molecular metabolism vol. 5,3 (2016): 184-197. doi: https://doi.org/10.1016/j.molmet.2015.12.002
de Castro Barbosa T, Ingerslev LR, Alm PS, Versteyhe S, Massart J, Rasmussen M, Donkin I, Sjögren R, Mudry JM, Vetterli L, Gupta S, Krook A, Zierath JR, Barrès R. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. Mol Metab. 2015 Dec 25;5(3):184-197. doi: 10.1016/j.molmet.2015.12.002. eCollection 2016 Mar. PMID: 26977389; PMCID: PMC4770269.
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Mol Metab. 2015 Dec 25;5(3):184-197. doi: 10.1016/j.molmet.2015.12.002. eCollection 2016 Mar.

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

Molecular metabolism

Thais de Castro Barbosa, Lars R Ingerslev, Petter S Alm, Soetkin Versteyhe, Julie Massart, Morten Rasmussen, Ida Donkin, Rasmus Sjögren, Jonathan M Mudry, Laurène Vetterli, Shashank Gupta, Anna Krook, Juleen R Zierath, Romain Barrès

Affiliations

  1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
  2. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  3. Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
  4. Department of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 76 Stockholm, Sweden.
  5. Department of Veterinary Disease Biology, University of Copenhagen, 1870 Frederiksberg, Denmark.
  6. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark; Department of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden; Department of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 76 Stockholm, Sweden.
  7. The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: [email protected].

PMID: 26977389 PMCID: PMC4770269 DOI: 10.1016/j.molmet.2015.12.002

Abstract

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.

Keywords: DNA methylation; Epigenetics; Obesity; Spermatozoa; microRNA

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