Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis

Endocrinology. 2010 Sep;151(9):4573-82. doi: 10.1210/en.2010-0511. Epub 2010 Jul 21.


Type 2 deiodinase (D2), which is highly expressed in brown adipose tissue (BAT), is an enzyme that amplifies thyroid hormone signaling in individual cells. Mice with inactivation of the D2 pathway (D2KO) exhibit dramatically impaired thermogenesis in BAT, leading to hypothermia during cold exposure and a greater susceptibility to diet-induced obesity. This was interpreted as a result of defective acute activation of BAT D2. Here we report that the adult D2KO BAT has a permanent thermogenic defect that stems from impaired embryonic BAT development. D2KO embryos have normal serum T3 but due to lack of D2-generated T3 in BAT, this tissue exhibits decreased expression of genes defining BAT identity [i.e. UCP1, PGC-1alpha and Dio2 (nonfunctional)], which results in impaired differentiation and oxidative capacity. Coinciding with a reduction of these T3-responsive genes, there is oxidative stress that in a cell model of brown adipogenesis can be linked to decreased insulin signaling and decreased adipogenesis. This discovery highlights the importance of deiodinase-controlled thyroid hormone signaling in BAT development, where it has important metabolic repercussions for energy homeostasis in adulthood.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acclimatization / genetics
  • Acclimatization / physiology
  • Adipocytes / cytology
  • Adipocytes / metabolism
  • Adipogenesis / genetics
  • Adipogenesis / physiology
  • Adipose Tissue, Brown / embryology
  • Adipose Tissue, Brown / growth & development
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • Blotting, Western
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Embryo, Mammalian / embryology
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / physiology
  • Female
  • Gene Expression Regulation, Developmental
  • Iodide Peroxidase / genetics
  • Iodide Peroxidase / metabolism*
  • Iodothyronine Deiodinase Type II
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxygen Consumption / genetics
  • Oxygen Consumption / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Temperature
  • Thermogenesis / genetics
  • Thermogenesis / physiology*
  • Thyroid Hormones / blood
  • Thyroid Hormones / metabolism*
  • Time Factors


  • Thyroid Hormones
  • Iodide Peroxidase