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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.<\/jats:p>","DOI":"10.1071\/rd16494","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T23:58:21Z","timestamp":1501718301000},"page":"430-441","source":"Crossref","is-referenced-by-count":2,"title":["Tissue cell stress response to obesity and its interaction with late gestation diet"],"prefix":"10.1071","volume":"30","author":[{"given":"Vivek","family":"Saroha","sequence":"first","affiliation":[{"name":"AEarly Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neele S.","family":"Dellschaft","sequence":"additional","affiliation":[{"name":"AEarly Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duane H.","family":"Keisler","sequence":"additional","affiliation":[{"name":"DDepartment of Animal Science, University of Missouri, Columbia, MO 65211, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Gardner","sequence":"additional","affiliation":[{"name":"CSchool of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, Nottingham LE12 5RD, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Budge","sequence":"additional","affiliation":[{"name":"AEarly Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain P.","family":"Sebert","sequence":"additional","affiliation":[{"name":"AEarly Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK."},{"name":"ECentre for Life-Course Health Research, and Biocentre Oulu, University of Oulu, Aapistie 5B, 90014 Oulu, Finland."},{"name":"FDepartment of Genomics of Complex Diseases, Imperial College London, London, UK."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael E.","family":"Symonds","sequence":"additional","affiliation":[{"name":"AEarly Life Research Unit, Academic Division of Child Health, Obstetrics and Gynaecology, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK."},{"name":"BNottingham Digestive Disease Centre and Biomedical Research Unit, School of Medicine, Queen\u2019s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK."},{"name":"GCorresponding author. 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