Chronic high-fat diet in fathers programs β 2-cell dysfunction in female rat offspring

Sheau Fang Ng, Ruby C Y Lin, D. Ross Laybutt, Romain Barres, Julie A. Owens, Margaret J. Morris

Research output: Contribution to journalArticle

800 Citations (Scopus)

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 2-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.

Original languageEnglish
Pages (from-to)963-966
Number of pages4
JournalNature
Volume467
Issue number7318
DOIs
Publication statusPublished - 21 Oct 2010
Externally publishedYes

Fingerprint

High Fat Diet
Fathers
Adiposity
Genes
Obesity
Wnt Signaling Pathway
Glucose Intolerance
Pediatric Obesity
Adult Children
Cytoskeleton
Islets of Langerhans
Type 2 Diabetes Mellitus
Insulin Resistance
Cations
Mammals
Cell Cycle
Adenosine Triphosphate
Body Weight
Mothers
Insulin

ASJC Scopus subject areas

  • General

Cite this

Ng, S. F., Lin, R. C. Y., Laybutt, D. R., Barres, R., Owens, J. A., & Morris, M. J. (2010). Chronic high-fat diet in fathers programs β 2-cell dysfunction in female rat offspring. Nature, 467(7318), 963-966. https://doi.org/10.1038/nature09491

Chronic high-fat diet in fathers programs β 2-cell dysfunction in female rat offspring. / Ng, Sheau Fang; Lin, Ruby C Y; Laybutt, D. Ross; Barres, Romain; Owens, Julie A.; Morris, Margaret J.

In: Nature, Vol. 467, No. 7318, 21.10.2010, p. 963-966.

Research output: Contribution to journalArticle

Ng, SF, Lin, RCY, Laybutt, DR, Barres, R, Owens, JA & Morris, MJ 2010, 'Chronic high-fat diet in fathers programs β 2-cell dysfunction in female rat offspring', Nature, vol. 467, no. 7318, pp. 963-966. https://doi.org/10.1038/nature09491
Ng SF, Lin RCY, Laybutt DR, Barres R, Owens JA, Morris MJ. Chronic high-fat diet in fathers programs β 2-cell dysfunction in female rat offspring. Nature. 2010 Oct 21;467(7318):963-966. https://doi.org/10.1038/nature09491
Ng, Sheau Fang ; Lin, Ruby C Y ; Laybutt, D. Ross ; Barres, Romain ; Owens, Julie A. ; Morris, Margaret J. / Chronic high-fat diet in fathers programs β 2-cell dysfunction in female rat offspring. In: Nature. 2010 ; Vol. 467, No. 7318. pp. 963-966.
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