Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring
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 indu...
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| Format: | Article |
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BioScientifica
2015
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| Online Access: | https://eprints.nottingham.ac.uk/28885/ |
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| author | Dellschaft, Neele S. Alexandre-Gouabau, Marie-Cecile Gardner, David S. Antignac, Jean-Philippe Keisler, Duane H. Budge, Helen Symonds, Michael E. Sebert, Sylvain P. |
| author_facet | Dellschaft, Neele S. Alexandre-Gouabau, Marie-Cecile Gardner, David S. Antignac, Jean-Philippe Keisler, Duane H. Budge, Helen Symonds, Michael E. Sebert, Sylvain P. |
| author_sort | Dellschaft, Neele S. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:03:55Z |
| format | Article |
| id | nottingham-28885 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T19:03:55Z |
| publishDate | 2015 |
| publisher | BioScientifica |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-288852017-10-13T19:53:51Z https://eprints.nottingham.ac.uk/28885/ Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring Dellschaft, Neele S. Alexandre-Gouabau, Marie-Cecile Gardner, David S. Antignac, Jean-Philippe Keisler, Duane H. Budge, Helen Symonds, Michael E. Sebert, Sylvain P. 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. BioScientifica 2015-02-01 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/28885/1/Accepted%20preprint%20Nov%202014%20JOE-14-0600.full.pdf Dellschaft, Neele S., Alexandre-Gouabau, Marie-Cecile, Gardner, David S., Antignac, Jean-Philippe, Keisler, Duane H., Budge, Helen, 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 1479-6805 IUGR perinatal growth obesity appatite regulation insulin leptin cortisol metabolomics gene expression http://joe.endocrinology-journals.org/content/224/2/171 doi:10.1530/JOE-14-0600 doi:10.1530/JOE-14-0600 |
| spellingShingle | IUGR perinatal growth obesity appatite regulation insulin leptin cortisol metabolomics gene expression Dellschaft, Neele S. Alexandre-Gouabau, Marie-Cecile Gardner, David S. Antignac, Jean-Philippe Keisler, Duane H. Budge, Helen Symonds, Michael E. Sebert, Sylvain P. Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| title | Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| title_full | Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| title_fullStr | Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| title_full_unstemmed | Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| title_short | Effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| title_sort | effect of pre- and postnatal growth and post-weaning activity on glucose metabolism in the offspring |
| topic | IUGR perinatal growth obesity appatite regulation insulin leptin cortisol metabolomics gene expression |
| url | https://eprints.nottingham.ac.uk/28885/ https://eprints.nottingham.ac.uk/28885/ https://eprints.nottingham.ac.uk/28885/ |