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| Status |
Public on Jan 20, 2014 |
| Title |
Effects of dietary obesity in fathers on gene expression of fat in the female offspring (mRNA data) |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
The global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed β-cell ‘dysfunction’ in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet altered the expression of 211 pancreatic islet genes in adult female offspring (P < 0.001); genes belonged to 8 functional clusters, including calcium ion binding, primary metabolic processes and ATP binding, and organ/system development. Broader KEGG pathway analysis of 2014 genes differentially expressed at the P < 0.01 level further demonstrated involvement of insulin and calcium signaling, and MAPK pathways. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
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| Overall design |
F0 founders were male Sprague Dawley rats, divided into two groups: high fat (HF) and control. The HF fathers were given commercially prepared high-fat pellets (43% as fat), while the controls ate standard laboratory chow (9% as fat). The two groups of fathers had distinct phenotypes; the HF fathers were significantly heavier with increased adiposity, and they were also glucose intolerant and insulin resistant. At 15 weeks of age, fathers were mated with normal females consuming chow to generate the F1 offspring. Only female offspring were studied. Female offspring were weaned unto standard laboratory chow at 3 weeks. At 6 and 12 weeks, an intraperitoneal glucose tolerance test (IpGTT) was performed to measure blood glucose and insulin profile; at 11 weeks, an intraperitoneal insulin tolerance test was done. The body weight and adiposity of these offspring were not different between the two groups. The HF offspring had glucose intolerance and impaired glucose-induced insulin response, mainly at the acute phase, observed since 6 weeks. The IpITT was not different between groups. At 14 weeks, fat was harvested from the two groups of offspring.
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| Contributor(s) |
Morris MJ, Ng SF, Lin RC |
| Citation(s) |
24421403, 26484128 |
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| Submission date |
Nov 08, 2011 |
| Last update date |
Jul 10, 2018 |
| Contact name |
Margaret J Morris |
| E-mail(s) |
m.morris@unsw.edu.au
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| Phone |
+61293851560
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| Organization name |
University of New South Wales
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| Department |
School of Medical Sciences
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| Lab |
Head of Pharmacology
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| Street address |
University of New South Wales
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| City |
Wallace Wurth Building, Sydney |
| State/province |
NSW |
| ZIP/Postal code |
2052 |
| Country |
Australia |
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| Platforms (1) |
| GPL6247 |
[RaGene-1_0-st] Affymetrix Rat Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (13)
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| GSM829764 |
Control 656, fat mRNA |
| GSM829765 |
Control 658, fat mRNA |
| GSM829766 |
Control 662, fat mRNA |
| GSM829767 |
Control 664, fat mRNA |
| GSM829768 |
HFD 619, fat mRNA |
| GSM829769 |
HFD 620, fat mRNA |
| GSM829770 |
HFD 624, fat mRNA |
| GSM829771 |
HFD 629, fat mRNA |
| GSM829772 |
HFD 660, fat mRNA |
| GSM829773 |
HFD 663, fat mRNA |
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| This SubSeries is part of SuperSeries: |
| GSE33564 |
Effects of dietary obesity in fathers on gene expression of fat in the female offspring |
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| Relations |
| BioProject |
PRJNA154265 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE33551_RAW.tar |
56.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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