A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue
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Publication Date
2017-03-24Journal Title
Scientific Reports
ISSN
2045-2322
Publisher
Nature Publishing Group
Volume
7
Number
44949
Language
English
Type
Article
This Version
VoR
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de Almeida Faria, J., Duque-Guimarães, D., Carpenter, A., Loche, E., & Ozanne, S. (2017). A post-weaning obesogenic diet exacerbates the detrimental effects of maternal obesity on offspring insulin signaling in adipose tissue. Scientific Reports, 7 (44949)https://doi.org/10.1038/srep44949
Abstract
Previous studies have shown that maternal diet-induced obesity leads to increased risk of type 2 diabetes in offspring. The current study investigated if weaning onto an obesogenic diet exaggerated the detrimental effects of maternal diet-induced obesity in adipose tissue. Maternal obesity and offspring obesity led to reduced expression of key insulin signalling proteins, including insulin receptor substrate-1 (IRS-1). The effects of maternal obesity and offspring obesity were, generally, independent and additive. Irs1 mRNA levels were similar between all four groups of offspring, suggesting that in both cases post-transcriptional regulation was involved. Maternal diet-induced obesity increased miR-126 expression however levels of this miR were not influenced by a post-weaning obesogenic diet. In contrast, a post-weaning obesogenic diet was associated with increased levels of suppressor of cytokine signaling-1, implicating increased degradation of IRS-1 as an underlying mechanism. Our results suggest that whilst programmed reductions in IRS-1 are associated with increased levels of miR-126 and consequently reduced translation of Irs1 mRNA, the effects of a post-weaning obesogenic diet on IRS-1 are mediated by miR-126 independent mechanisms, including increased IRS-1 protein degradation. These divergent mechanisms explain why the combination of maternal obesity and offspring obesity leads to the most pronounced effects on offspring metabolism.
Sponsorship
The. Medical Research Council (MC_UU_12012/4), Biotechnology and Biological Sciences Research Council (BB/M001636/1), British Heart Foundation (PG/14/20/30769) and São Paulo Research Foundation (2014/17012-4 and 2014/20380-5) supported this research.
Funder references
MRC (MC_UU_12012/4)
BBSRC (BB/M001636/1)
British Heart Foundation (PG/14/20/30769)
British Heart Foundation (FS/09/029/27902)
Identifiers
External DOI: https://doi.org/10.1038/srep44949
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264040
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International