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Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues

Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabol...

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Autores principales: Guo, Chunming, Li, Cun, Myatt, Leslie, Nathanielsz, Peter W., Sun, Kang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609578/
https://www.ncbi.nlm.nih.gov/pubmed/23238295
http://dx.doi.org/10.2337/db12-0561
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author Guo, Chunming
Li, Cun
Myatt, Leslie
Nathanielsz, Peter W.
Sun, Kang
author_facet Guo, Chunming
Li, Cun
Myatt, Leslie
Nathanielsz, Peter W.
Sun, Kang
author_sort Guo, Chunming
collection PubMed
description Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings’ susceptibility to metabolic syndrome.
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spelling pubmed-36095782014-04-01 Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues Guo, Chunming Li, Cun Myatt, Leslie Nathanielsz, Peter W. Sun, Kang Diabetes Original Research Maternal nutrient reduction (MNR) during fetal development may predispose offspring to chronic disease later in life. Increased regeneration of active glucocorticoids by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in metabolic tissues is fundamental to the developmental programming of metabolic syndrome, but underlying mechanisms are unknown. Hexose-6-phosphate dehydrogenase (H6PD) generates NADPH, the cofactor for 11β-HSD1 reductase activity. CCAAT/enhancer binding proteins (C/EBPs) and the glucocorticoid receptor (GR) regulate 11β-HSD1 expression. We hypothesize that MNR increases expression of fetal C/EBPs, GR, and H6PD, thereby increasing expression of 11β-HSD1 and reductase activity in fetal liver and adipose tissues. Pregnant MNR baboons ate 70% of what controls ate from 0.16 to 0.9 gestation (term, 184 days). Cortisol levels in maternal and fetal circulations increased in MNR pregnancies at 0.9 gestation. MNR increased expression of 11β-HSD1; H6PD; C/EBPα, -β, -γ; and GR in female but not male perirenal adipose tissue and in male but not female liver at 0.9 gestation. Local cortisol level and its targets PEPCK1 and PPARγ increased correspondingly in adipose and liver tissues. C/EBPα and GR were found to be bound to the 11β-HSD1 promoter. In conclusion, sex- and tissue-specific increases of 11β-HSD1, H6PD, GR, and C/EBPs may contribute to sexual dimorphism in the programming of exaggerated cortisol regeneration in liver and adipose tissues and offsprings’ susceptibility to metabolic syndrome. American Diabetes Association 2013-04 2013-03-14 /pmc/articles/PMC3609578/ /pubmed/23238295 http://dx.doi.org/10.2337/db12-0561 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Guo, Chunming
Li, Cun
Myatt, Leslie
Nathanielsz, Peter W.
Sun, Kang
Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
title Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
title_full Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
title_fullStr Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
title_full_unstemmed Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
title_short Sexually Dimorphic Effects of Maternal Nutrient Reduction on Expression of Genes Regulating Cortisol Metabolism in Fetal Baboon Adipose and Liver Tissues
title_sort sexually dimorphic effects of maternal nutrient reduction on expression of genes regulating cortisol metabolism in fetal baboon adipose and liver tissues
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609578/
https://www.ncbi.nlm.nih.gov/pubmed/23238295
http://dx.doi.org/10.2337/db12-0561
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