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Cited by 1,327Birth, Development, and HealthPancreatic function and diabetesSperm and Testicular Function

Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring

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Ng, Sheau-Fang, Lin, Ruby C. Y., Laybutt, D. Ross, Barres, Romain, Owens, Julie A., Morris, Margaret J.·2010·Nature
DOI 10.1038/nature09491
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Abstract

The global prevalence of obesity is increasing across most ages in both sexes. This is contributing to the early emergence of type 2 diabetes and its related epidemic. Having either parent obese is an independent risk factor for childhood obesity. Although the detrimental impacts of diet-induced maternal obesity on adiposity and metabolism in offspring are well established, the extent of any contribution of obese fathers is unclear, particularly the role of non-genetic factors in the causal pathway. Here we show that paternal high-fat-diet (HFD) exposure programs β-cell 'dysfunction' in rat F(1) female offspring. Chronic HFD consumption in Sprague-Dawley fathers induced increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had an early onset of impaired insulin secretion and glucose tolerance that worsened with time, and normal adiposity. Paternal HFD altered the expression of 642 pancreatic islet genes in adult female offspring (P < 0.01); genes belonged to 13 functional clusters, including cation and ATP binding, cytoskeleton and intracellular transport. Broader pathway analysis of 2,492 genes differentially expressed (P < 0.05) demonstrated involvement of calcium-, MAPK- and Wnt-signalling pathways, apoptosis and the cell cycle. Hypomethylation of the Il13ra2 gene, which showed the highest fold difference in expression (1.76-fold increase), was demonstrated. This is the first report in mammals of non-genetic, intergenerational transmission of metabolic sequelae of a HFD from father to offspring.

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Crossref · 10.1038/nature09491

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3 of 3 references verified0 citation errors · 0 not checkable

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  • This suggests a paternal transmission of metabolic risk independent of maternal environment.

    “This suggested a paternal transmission of metabolic risk independent of maternal environment [178].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [178]

  • Parental health and diet, not only during pregnancy but also prior to conception, play a crucial role in shaping disease susceptibility across generations.

    “The concept of transgenerational inheritance thus expands the traditional view of fetal programming, emphasizing that parental health and diet—not only during pregnancy but also prior to conception—play a crucial role in shaping disease susceptibility across generations [73,169,175,177,178,179].”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [178]

  • Both maternal and paternal nutritional environments before and during conception can profoundly influence offspring metabolic programming through heritable epigenetic mechanisms.

    “Together, these findings demonstrate that both maternal and paternal nutritional environments before and during conception can profoundly influence offspring metabolic programming through heritable epigenetic mechanisms.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [178]

  • Male mice fed an HFD developed obesity, insulin resistance, and hepatic steatosis, and when mated with control-fed females, their female offspring exhibited impaired glucose tolerance and a reduction in pancreatic β-cell mass, despite normal body weight.

    “Ng et al., who showed that male mice fed an HFD developed obesity, insulin resistance, and hepatic steatosis, and when mated with control-fed females, their female offspring exhibited impaired glucose tolerance and a reduction in pancreatic β-cell mass, despite normal body weight.”

    From Maternal Overnutrition and Fetal Programming: Long-Term Metabolic, Cognitive, and Epigenetic Consequences (2026) · cites this paper as [178]

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Authors
Ng, S.-F., Lin, R. C. Y., Laybutt, D. R., Barres, R., Owens, J. A., & Morris, M. J.
Affiliations
  • UNSW Sydney (AU)
  • Garvan Institute of Medical Research (AU)
  • The University of Adelaide (AU)
Corresponding author
Morris, Margaret J.
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2010-10
Volume
467
Issue
7318
Pages
963-966
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature09491
OpenAlex
W2130597092
Cited by
1,327
References
3
Citations by year
2026: 30 · 2025: 43 · 2024: 58 · 2023: 54 · 2022: 70 · 2021: 68 · 2020: 109 · 2019: 81 · 2018: 95 · 2017: 98 · 2016: 96 · 2015: 121 · 2014: 126 · 2013: 92 · 2012: 107
FWCI
80.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • UNSWorks (UNSW Sydney) (submittedVersion, cc-by-nc-nd)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
Keywords
intergenerational epigenetic inheritance, beta-cell dysfunction, impaired insulin secretion, impaired glucose tolerance, type 2 diabetes, childhood obesity, calcium signaling, MAPK signaling, Wnt signaling, apoptosis, male obesity
MeSH terms
Insulin Secretion, Adenosine Triphosphate, Aging, Animals, Body Weight, Cations, Cell Cycle, Cytoskeleton, Diabetes Mellitus, Type 2, Diet, Dietary Fats, Fathers, Female, Gene Expression Regulation, Glucose, Glucose Tolerance Test, Homeostasis, Insulin, Litter Size, Male, Obesity, Signal Transduction, Rats, Sprague-Dawley, Apoptosis, Glucose Intolerance, Paternal Exposure, DNA Methylation, Gene Expression Profiling, Epigenesis, Genetic, Adiposity, Insulin-Secreting Cells, Rats

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