Evidence map›Paper›PMID 26977389›Full record

ArticleMolecular metabolism2016

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

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 and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 196 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
196citing papers in PubMed, 2 pooled it
14.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

196 citing papers in PubMed, 2 syntheses or guidelines pooled it, 413 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Article
  4. Review
  5. Article
  6. Article
  7. Paternal Circadian Disruption Impairs Offspring Cognition via Sperm microRNAs.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  8. Article
  9. Review
  10. A Review of the Effects of Maternal and Paternal Obesity on Neurodevelopmental Disorders and Related Neurobiology in Rodent and Human Offspring.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. The Correlation betweenInternational journal of fertility & sterility · 2026
    Article
  18. Environmental and Genetic Perturbations of the Sperm Epigenome.Advances in experimental medicine and biology · 2026
    Review
  19. Phthalate exposure to adult mice alters non-coding RNAs in cauda epididymosomes.Environmental pollution (Barking, Essex : 1987) · 2025
    Article
  20. Review

136 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 2 countries.

Thais de Castro BarbosaThe 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.
Lars R IngerslevThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Petter S AlmDepartment of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Soetkin VersteyheThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Julie MassartDepartment of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Morten RasmussenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Ida DonkinThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
Rasmus SjögrenDepartment of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Jonathan M MudryDepartment of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Laurène VetterliDepartment of Molecular Medicine and Surgery, Section of Integrative Physiology, Karolinska Institutet, 171 76 Stockholm, Sweden.
Shashank GuptaDepartment of Veterinary Disease Biology, University of Copenhagen, 1870 Frederiksberg, Denmark.
Anna KrookDepartment of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Juleen R ZierathThe 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.
Romain BarrèsThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark. Electronic address: barres@sund.ku.dk.
University of Copenhagen · DKKarolinska Institutet · SE

Funding

European Research Council 233285
6 · The paper itself

Abstract

objectivesChronic 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.

methodsF0-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.

resultsNewborn 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.

conclusionOur results provide insight into mechanisms by which HFD transgenerationally reprograms the epigenome of sperm cells, thereby affecting metabolic tissues of offspring throughout two generations.

Indexed as

DNA methylationEpigeneticsmicroRNAObesitySpermatozoa

Identifiers

PMID26977389
PMCPMC4770269
OpenAlexW2203634181

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.