Dioxins, the aryl hydrocarbon receptor and the central regulation of energy balance |
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Authors: | Jere Lind n, Sanna Lensu, Jouko Tuomisto,Raimo Pohjanvirta |
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Affiliation: | a Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki, Finland;b Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki, Finland;c Department of Environmental Health, National Institute for Health and Welfare, P.O. Box 95, FI-70701 Kuopio, Finland;d Faculty of Health Sciences, The School of Pharmacy, University of Eastern Finland, P.O. Box 1611, FI-70211 Kuopio, Finland |
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Abstract: | Dioxins are ubiquitous environmental contaminants that have attracted toxicological interest not only for the potential risk they pose to human health but also because of their unique mechanism of action. This mechanism involves a specific, phylogenetically old intracellular receptor (the aryl hydrocarbon receptor, AHR) which has recently proven to have an integral regulatory role in a number of physiological processes, but whose endogenous ligand is still elusive. A major acute impact of dioxins in laboratory animals is the wasting syndrome, which represents a puzzling and dramatic perturbation of the regulatory systems for energy balance. A single dose of the most potent dioxin, TCDD, can permanently readjust the defended body weight set-point level thus providing a potentially useful tool and model for physiological research. Recent evidence of response-selective modulation of AHR action by alternative ligands suggests further that even therapeutic implications might be possible in the future. |
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Keywords: | Dioxins TCDD 2,3,7,8-tetrachlorodibenzo-p-dioxin Aryl hydrocarbon receptor Food intake Energy balance Body weight Wasting syndrome Central nervous system |
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