University of Oulu

Reproduction, Fertility and Development 30(3) 430-441

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

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Author: Saroha, Vivek1; Dellschaft, Neele S.1; Keisler, Duane H.2;
Organizations: 1Early Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
2Department of Animal Science, University of Missouri, Columbia, MO 65211, USA
3School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, Nottingham LE12 5RD, UK
4Centre for Life-Course Health Research, and Biocentre Oulu, University of Oulu, Aapistie 5B, 90014 Oulu, Finland
5Department of Genomics of Complex Diseases, Imperial College London, London, UK
6Nottingham Digestive Disease Centre and Biomedical Research Unit, School of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
Persistent link:
Language: English
Published: CSIRO Publishing, 2018
Publish Date: 2019-09-19


Intrauterine growth restriction in late pregnancy can contribute to adverse long-term metabolic health in the offspring. In the present study we used 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 (~147 days). After weaning (~3 months of age), the 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, regardless of maternal diet. Molecular markers of stress and autophagy in liver and adipose tissue were increased with obesity, with gene expression of hepatic glucose-related protein 78 (Grp78) and omental activation transcription factor 6 (Atf6), Grp78 and ER stress degradation enhancer molecule 1 (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.

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Series: Reproduction, fertility and development
ISSN: 1031-3613
ISSN-E: 1448-5990
ISSN-L: 1031-3613
Volume: 30
Issue: 3
Pages: 430 - 441
DOI: 10.1071/RD16494
Type of Publication: A1 Journal article – refereed
Field of Science: 3124 Neurology and psychiatry
3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the European Union Sixth Framework Program for Research and Technical Development of the European Community, The Early Nutrition Programming Project FOOD-CT-2005-007036, the Nutricia Research Foundation, and the Nottingham Respiratory Biomedical Research Unit. S.P.S. was also supported by a Wellcome Trust Value-in-People award.
Copyright information: © Csiro Publishing. This is the peer reviewed version of the following article: Reproduction, Fertility and Development 30(3) 430-441, which has been published in final form at