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Tissue cell stress response to obesity and its interaction with late gestational diet

Saroha, Vivek; Dellschaft, Neele S.; Keisler, Duane H.; Gardner, David S.; Budge, Helen; Sebert, Sylvain P.; Symonds, Michael E.

Authors

Vivek Saroha

Neele S. Dellschaft

Duane H. Keisler

David S. Gardner

HELEN BUDGE HELEN.BUDGE@NOTTINGHAM.AC.UK
Professor of Neonatal Medicine

Sylvain P. Sebert

Michael E. Symonds



Abstract

Intra-uterine growth restriction in late pregnancy can contribute to adverse long term metabolic health in the offspring. We utilised an animal (sheep) model of maternal dietary manipulation in late pregnancy, combined with exposure of the offspring to a low activity, obesogenic environment after weaning, to characterise the effects on glucose homeostasis. Dizygotic twin-pregnant sheep were either fed to 60% of requirements (nutrient restriction (R)) or fed ad libitum (~ 140% of requirements (A)) from 110 days gestation until term (~147d). After weaning (~3 months of age), their offspring were kept in either a standard (in order to remain lean) or low activity, obesogenic environment. R mothers gained less weight and produced smaller offspring. As adults, obese offspring were heavier and fatter with reduced glucose tolerance, irrespective of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expression of hepatic Grp78 and of omental Atf6, Grp78 and Edem1 only being increased in R offspring. In conclusion, the adverse effect of juvenile onset obesity on insulin responsive tissues can be amplified by previous exposure to a suboptimal nutritional environment in utero, thereby contributing to earlier onset of insulin resistance.

Citation

Saroha, V., Dellschaft, N. S., Keisler, D. H., Gardner, D. S., Budge, H., Sebert, S. P., & Symonds, M. E. (2018). Tissue cell stress response to obesity and its interaction with late gestational diet. Reproduction, Fertility and Development, 30, https://doi.org/10.1071/RD16494

Journal Article Type Article
Acceptance Date Jul 8, 2017
Online Publication Date Aug 3, 2017
Publication Date Jan 30, 2018
Deposit Date Jul 26, 2017
Publicly Available Date Aug 3, 2017
Journal Reproduction, Fertility and Development
Print ISSN 1031-3613
Electronic ISSN 1448-5990
Publisher CSIRO Publishing
Peer Reviewed Peer Reviewed
Volume 30
DOI https://doi.org/10.1071/RD16494
Keywords adipose tissue, appetite, growth, nutrition
Public URL http://eprints.nottingham.ac.uk/id/eprint/44428
Publisher URL http://www.publish.csiro.au/rd/RD16494
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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RFD Final accepted version July 2017.pdf (542 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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