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Journal of Obesity
Volume 2014 (2014), Article ID 829862, 9 pages
Research Article

Intrauterine Growth Restriction Increases TNFα and Activates the Unfolded Protein Response in Male Rat Pups

1Division of Nutrition, University of Utah, Salt Lake City, UT 84158, USA
2Department of Pediatrics, University of Utah, Salt Lake City, UT 84158, USA
3Division of Neonatology, University of Utah, P.O. Box 581289, Salt Lake City, UT 84158, USA

Received 25 November 2013; Revised 4 February 2014; Accepted 12 March 2014; Published 6 April 2014

Academic Editor: Michel M. Murr

Copyright © 2014 Emily S. Riddle et al. 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.


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.