Tissue cell stress response to obesity and its interaction with late gestation diet
Vivek Saroha A , Neele S. Dellschaft A , Duane H. Keisler D , David S. Gardner C , Helen Budge A , Sylvain P. Sebert A E F and Michael E. Symonds A B G
+ Author Affiliations
- Author Affiliations
A Early 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.
B Nottingham Digestive Disease Centre and Biomedical Research Unit, School of Medicine, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
C School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, Nottingham LE12 5RD, UK.
D Department of Animal Science, University of Missouri, Columbia, MO 65211, USA.
E Centre for Life-Course Health Research, and Biocentre Oulu, University of Oulu, Aapistie 5B, 90014 Oulu, Finland.
F Department of Genomics of Complex Diseases, Imperial College London, London, UK.
G Corresponding author. Email: michael.symonds@nottingham.ac.uk
Reproduction, Fertility and Development 30(3) 430-441 https://doi.org/10.1071/RD16494
Submitted: 7 December 2016 Accepted: 8 July 2017 Published: 3 August 2017
Abstract
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.
Additional keywords: adipose tissue, appetite, growth, nutrition.
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