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

Maria Sjögren, Anneke Alkemade, Jens Mittag, Kristina Nordström, Abram Katz, Björn Rozell, Håkan Westerblad, Anders Arner, Björn Vennström

Abstract

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.

Original languageEnglish
JournalThe EMBO journal
Volume26
Issue number21
Pages (from-to)4535-45
Number of pages11
ISSN0261-4189
DOIs
Publication statusPublished - 2007

Fingerprint

Dive into the research topics of 'Hypermetabolism in mice caused by the central action of an unliganded thyroid hormone receptor alpha1'. Together they form a unique fingerprint.

Cite this