Article
- The EMBO Journal (2007) 26, 4535 - 4545
- doi:10.1038/sj.emboj.7601882
Published online: 11 October 2007
Subject Category:
Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor 
1
Maria Sjögren1,a, Anneke Alkemade1,a, Jens Mittag1, Kristina Nordström1, Abram Katz2, Björn Rozell3, Håkan Westerblad2, Anders Arner2 and Björn Vennström1
- Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
- Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
- Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institutet, Huddinge, Sweden
Correspondence to:
Björn Vennström, Department of Cell and Molecular Biology, Karolinska Institutet, Box 285, Stockholm 171 77, Sweden. Tel.: +46 8 52487350; Fax: +46 8 348135; E-mail: Bjorn.Vennstrom@ki.se
aThese authors contributed equally to this work
Received 3 August 2007; Accepted 18 September 2007
Abstract
Thyroid hormone, via its nuclear receptors TR
and TR
, controls metabolism by acting locally in peripheral tissues and centrally by regulating sympathetic signaling. We have defined aporeceptor regulation of metabolism by using mice heterozygous for a mutant TR1 with low affinity to T3. The animals were hypermetabolic, showing strongly reduced fat depots, hyperphagia and resistance to diet-induced obesity accompanied by induction of genes involved in glucose handling and fatty acid metabolism in liver and adipose tissues. Increased lipid mobilization and -oxidation occurred in adipose tissues, whereas blockade of sympathetic signaling to brown adipose tissue normalized the metabolic phenotype despite a continued perturbed hormone signaling in this cell type. The results define a novel and important role for the TR1 aporeceptor in governing metabolic homeostasis. Furthermore, the data demonstrate that a nuclear hormone receptor affecting sympathetic signaling can override its autonomous effects in peripheral tissues.
Keywords:
- metabolism,
- sympathetic nervous system,
- thermogenesis,
- thyroid hormone receptor
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