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

Research output: Contribution to journal › Journal article › Research › peer-review

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High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. / de Castro Barbosa, Thais; Ingerslev, Lars R; Alm, Petter S; Versteyhe, Soetkin; Massart, Julie; Rasmussen, Morten; Donkin, Ida; Sjögren, Rasmus; Mudry, Jonathan M; Vetterli, Laurène; Gupta, Shashank; Krook, Anna; Zierath, Juleen R; Barrès, Romain.

In: Molecular Metabolism, Vol. 5, No. 3, 03.2016, p. 184-97.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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 2016, 'High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring', Molecular Metabolism, vol. 5, no. 3, pp. 184-97. https://doi.org/10.1016/j.molmet.2015.12.002

APA

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), 184-97. https://doi.org/10.1016/j.molmet.2015.12.002

Vancouver

de Castro Barbosa T, Ingerslev LR, Alm PS, Versteyhe S, Massart J, Rasmussen M et al. High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. Molecular Metabolism. 2016 Mar;5(3):184-97. https://doi.org/10.1016/j.molmet.2015.12.002

Author

de Castro Barbosa, Thais ; Ingerslev, Lars R ; Alm, Petter S ; Versteyhe, Soetkin ; Massart, Julie ; Rasmussen, Morten ; Donkin, Ida ; Sjögren, Rasmus ; Mudry, Jonathan M ; Vetterli, Laurène ; Gupta, Shashank ; Krook, Anna ; Zierath, Juleen R ; Barrès, Romain. / High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring. In: Molecular Metabolism. 2016 ; Vol. 5, No. 3. pp. 184-97.

Bibtex

@article{9b2d2677f64f4e848e21b1d52a53dba4,
title = "High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring",
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.",
author = "{de Castro Barbosa}, Thais and Ingerslev, {Lars R} and Alm, {Petter S} and Soetkin Versteyhe and Julie Massart and Morten Rasmussen and Ida Donkin and Rasmus Sj{\"o}gren and Mudry, {Jonathan M} and Laur{\`e}ne Vetterli and Shashank Gupta and Anna Krook and Zierath, {Juleen R} and Romain Barr{\`e}s",
year = "2016",
month = mar,
doi = "10.1016/j.molmet.2015.12.002",
language = "English",
volume = "5",
pages = "184--97",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",
number = "3",

}

RIS

TY - JOUR

T1 - High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring

AU - de Castro Barbosa, Thais

AU - Ingerslev, Lars R

AU - Alm, Petter S

AU - Versteyhe, Soetkin

AU - Massart, Julie

AU - Rasmussen, Morten

AU - Donkin, Ida

AU - Sjögren, Rasmus

AU - Mudry, Jonathan M

AU - Vetterli, Laurène

AU - Gupta, Shashank

AU - Krook, Anna

AU - Zierath, Juleen R

AU - Barrès, Romain

PY - 2016/3

Y1 - 2016/3

N2 - 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.

AB - 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.

U2 - 10.1016/j.molmet.2015.12.002

DO - 10.1016/j.molmet.2015.12.002

M3 - Journal article

C2 - 26977389

VL - 5

SP - 184

EP - 197

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

IS - 3

ER -

ID: 159743593