View the Current Issue

Article

  • The EMBO Journal (2007) 26, 4535 - 4545
  • doi:10.1038/sj.emboj.7601882

Published online: 11 October 2007

Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1

Maria Sjögren1,a, Anneke Alkemade1,a, Jens Mittag1, Kristina Nordström1, Abram Katz2, Björn Rozell3, Håkan Westerblad2, Anders Arner2 and Björn Vennström1

  1. Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
  2. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
  3. 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

Thyroid hormone, via its nuclear receptors TRalpha and TRbeta, 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 TRalpha1 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 beta-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 TRalpha1 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
Top

MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated

REVIEWS

The stressed hippocampus, synaptic plasticity and lost memories

Nature Reviews Neuroscience Review (01 Jun 2002)

RESEARCH

FOXO3a mediates the androgen-dependent regulation of FLIP and contributes to TRAIL-induced apoptosis of LNCaP cells

Oncogene Original Article

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

Neuropsychopharmacology Original Article

Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1

Nature Medicine Article (01 Oct 2001)

Developmental origins of obesity: a sympathoadrenal perspective

International Journal of Obesity Original Article