Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring

Dellschaft, Neele S. and Alexandre-Gouabau, Marie-Cecile and Gardner, David S. and Antignac, Jean-Philippe and Keisler, Duane H. and Budge, Helen and Symonds, Michael E. and Sebert, Sylvain P. (2015) Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring. Journal of Endocrinology, 224 (2). pp. 171-182. ISSN 0022-0795

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Maternal caloric restriction during late gestation reduces birth weight, but whether long-term adverse metabolic outcomes of intra-uterine growth retardation (IUGR) are dependent on either accelerated postnatal growth or exposure to an obesogenic environment after weaning is not established. We induced IUGR in twin-pregnant sheep using a 40% maternal caloric restriction commencing from 110 days of gestation until term (∼147 days), compared with mothers fed to 100% of requirements. Offspring were reared either as singletons to accelerate postnatal growth or as twins to achieve standard growth. To promote an adverse phenotype in young adulthood, after weaning, offspring were reared under a low-activity obesogenic environment with the exception of a subgroup of IUGR offspring, reared as twins, maintained in a standard activity environment. We assessed glucose tolerance together with leptin and cortisol responses to feeding in young adulthood when the hypothalamus was sampled for assessment of genes regulating appetite control, energy and endocrine sensitivity. Caloric restriction reduced maternal plasma glucose, raised non-esterified fatty acids, and changed the metabolomic profile, but had no effect on insulin, leptin, or cortisol. IUGR offspring whose postnatal growth was enhanced and were obese showed insulin and leptin resistance plus raised cortisol. This was accompanied by increased hypothalamic gene expression for energy and glucocorticoid sensitivity. These long-term adaptations were reduced but not normalized in IUGR offspring whose postnatal growth was not accelerated and remained lean in a standard post-weaning environment. IUGR results in an adverse metabolic phenotype, especially when postnatal growth is enhanced and offspring progress to juvenile-onset obesity.

Item Type: Article
Additional Information: Disclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication in the Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at: doi: 10.1530/JOE-14-0600, 2014.
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Identification Number: https://doi.org/10.1530/JOE-14-0600
Depositing User: Gardner, David
Date Deposited: 06 Aug 2015 14:51
Last Modified: 17 Sep 2016 01:44
URI: http://eprints.nottingham.ac.uk/id/eprint/29285

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