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Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups
Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinfla...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997936/ https://www.ncbi.nlm.nih.gov/pubmed/24804087 http://dx.doi.org/10.1155/2014/829862 |
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author | Riddle, Emily S. Campbell, Michael S. Lang, Brook Y. Bierer, Ryann Wang, Yan Bagley, Heidi N. Joss-Moore, Lisa A. |
author_facet | Riddle, Emily S. Campbell, Michael S. Lang, Brook Y. Bierer, Ryann Wang, Yan Bagley, Heidi N. Joss-Moore, Lisa A. |
author_sort | Riddle, Emily S. |
collection | PubMed |
description | Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNFα). TNFα contributes to adipocyte inflammation and impaired insulin signaling. TNFα has also been implicated in the activation of the unfolded protein response (UPR), which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNFα, TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2α, and Ddit3) prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1) increased circulating and adipose TNFα, (2) increased mRNA levels of UPR components as well as p-eIF2a, and (3) impaired glucose tolerance after observed TNFα increased and after UPR activation. We speculate that programmed dysregulation of TNFα and UPR contributed to the development of glucose intolerance in male IUGR rats. |
format | Online Article Text |
id | pubmed-3997936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-39979362014-05-06 Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups Riddle, Emily S. Campbell, Michael S. Lang, Brook Y. Bierer, Ryann Wang, Yan Bagley, Heidi N. Joss-Moore, Lisa A. J Obes Research Article Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNFα). TNFα contributes to adipocyte inflammation and impaired insulin signaling. TNFα has also been implicated in the activation of the unfolded protein response (UPR), which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNFα, TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2α, and Ddit3) prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1) increased circulating and adipose TNFα, (2) increased mRNA levels of UPR components as well as p-eIF2a, and (3) impaired glucose tolerance after observed TNFα increased and after UPR activation. We speculate that programmed dysregulation of TNFα and UPR contributed to the development of glucose intolerance in male IUGR rats. Hindawi Publishing Corporation 2014 2014-04-06 /pmc/articles/PMC3997936/ /pubmed/24804087 http://dx.doi.org/10.1155/2014/829862 Text en Copyright © 2014 Emily S. Riddle et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Riddle, Emily S. Campbell, Michael S. Lang, Brook Y. Bierer, Ryann Wang, Yan Bagley, Heidi N. Joss-Moore, Lisa A. Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups |
title | Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups |
title_full | Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups |
title_fullStr | Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups |
title_full_unstemmed | Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups |
title_short | Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups |
title_sort | intrauterine growth restriction increases tnfα and activates the unfolded protein response in male rat pups |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997936/ https://www.ncbi.nlm.nih.gov/pubmed/24804087 http://dx.doi.org/10.1155/2014/829862 |
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