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Int. J. Mol. Sci. 2014, 15(8), 13938-13966; doi:10.3390/ijms150813938

Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain

1
Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland
2
Department of Biology of Physical Activity, Faculty of Sport and Health Sciences, University of Jyväskylä, P.O. Box 35, FI-40014 Jyväskylä, Finland
3
Department of Environmental Health, National Institute for Health and Welfare (THL), P.O. Box 95, FI-70701 Kuopio, Finland
4
Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 Helsinki, Finland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 14 May 2014 / Revised: 24 July 2014 / Accepted: 29 July 2014 / Published: 12 August 2014
(This article belongs to the Special Issue Mechanisms of Toxicity of Dioxins and Related Compounds)
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Abstract

One of the hallmarks of the acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a drastically reduced feed intake by an unknown mechanism. To further elucidate this wasting syndrome, we followed the effects of a single large dose (100 μg/kg) of TCDD on the serum levels of several energy balance-influencing hormones, clinical chemistry variables, and hepatic aryl hydrocarbon receptor (AHR) expression in two rat strains that differ widely in their TCDD sensitivities, for up to 10 days. TCDD affected most of the analytes in sensitive Long-Evans rats, while there were few alterations in the resistant Han/Wistar strain. However, analyses of feed-restricted unexposed Long-Evans rats indicated several of the perturbations to be secondary to energy deficiency. Notable increases in ghrelin and glucagon occurred in TCDD-treated Long-Evans rats alone, which links these hormones to the wasting syndrome. The newly found energy balance regulators, insulin-like growth factor 1 and fibroblast growth factor 21 (FGF-21), appeared to function in concert in body weight loss-induced metabolic state, and FGF-21 was putatively linked to increased lipolysis induced by TCDD. Finally, we demonstrate a reverse set of changes in the AHR protein and mRNA response to TCDD and feed restriction, suggesting that AHR might function also as a physiological regulator, possibly involved in the maintenance of energy balance. View Full-Text
Keywords: 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; wasting syndrome; energy balance; hormones; acute toxicity; strain differences; AHR 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD; wasting syndrome; energy balance; hormones; acute toxicity; strain differences; AHR
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Lindén, J.; Lensu, S.; Pohjanvirta, R. Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) on Hormones of Energy Balance in a TCDD-Sensitive and a TCDD-Resistant Rat Strain. Int. J. Mol. Sci. 2014, 15, 13938-13966.

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