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

Jessica A. Hall, Scott Ribich, Marcelo A. Christoffolete, Gordana Simovic, Mayrin Correa-Medina, Mary Elizabeth Patti, Antonio C. Bianco

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Abstract

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-1α 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.

Original languageEnglish
Pages (from-to)4573-4582
Number of pages10
JournalEndocrinology
Volume151
Issue number9
DOIs
StatePublished - Sep 1 2010

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Brown Adipose Tissue
Thermogenesis
Thyroid Hormones
Adipogenesis
Iodide Peroxidase
Hypothermia
Oxidative Stress
Homeostasis
Embryonic Structures
Obesity
Insulin
Diet
Gene Expression
Enzymes
Serum

ASJC Scopus subject areas

  • Endocrinology

Cite this

Hall, J. A., Ribich, S., Christoffolete, M. A., Simovic, G., Correa-Medina, M., Patti, M. E., & Bianco, A. C. (2010). Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology, 151(9), 4573-4582. https://doi.org/10.1210/en.2010-0511

Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. / Hall, Jessica A.; Ribich, Scott; Christoffolete, Marcelo A.; Simovic, Gordana; Correa-Medina, Mayrin; Patti, Mary Elizabeth; Bianco, Antonio C.

In: Endocrinology, Vol. 151, No. 9, 01.09.2010, p. 4573-4582.

Research output: Contribution to journalArticle

Hall, JA, Ribich, S, Christoffolete, MA, Simovic, G, Correa-Medina, M, Patti, ME & Bianco, AC 2010, 'Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis', Endocrinology, vol. 151, no. 9, pp. 4573-4582. https://doi.org/10.1210/en.2010-0511
Hall JA, Ribich S, Christoffolete MA, Simovic G, Correa-Medina M, Patti ME et al. Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology. 2010 Sep 1;151(9):4573-4582. https://doi.org/10.1210/en.2010-0511
Hall, Jessica A. ; Ribich, Scott ; Christoffolete, Marcelo A. ; Simovic, Gordana ; Correa-Medina, Mayrin ; Patti, Mary Elizabeth ; Bianco, Antonio C. / Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. In: Endocrinology. 2010 ; Vol. 151, No. 9. pp. 4573-4582.
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