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

Saroha, Vivek and Dellschaft, Neele S. and Keisler, Duane H. and Gardner, David S. and Budge, Helen and Sebert, Sylvain P. and Symonds, Michael E. (2017) Tissue cell stress response to obesity and its interaction with late gestation diet. Reproduction, Fertility and Development . ISSN 1448-5990

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: 10.1071/RD16494
Depositing User: Lashkova, Mrs Olga
Date Deposited: 11 Aug 2017 13:11
Last Modified: 18 Oct 2017 03:49
URI: http://eprints.nottingham.ac.uk/id/eprint/44859

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