The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue

Lucia A. De Jesus, Suzy D. Carvalho, Mirian O. Ribeiro, Mark Schneider, Sung Woo Kim, John W. Harney, P. Reed Larsen, Antonio C. Bianco

Research output: Contribution to journalArticle

314 Citations (Scopus)

Abstract

Type 2 iodothyronine deiodinase (D2) is a selenoenzyme, the product of the recently cloned cAMP-dependent Dio2 gene, which increases 10- to 50-fold during cold stress only in brown adipose tissue (BAT). Here we report that despite a normal plasma 3,5,3′-triiodothyronine (T3) concentration, coldexposed mice with targeted disruption of the Dio2 gene (Dio2-/-) become hypothermic due to impaired BAT thermogenesis and survive by compensatory shivering with consequent acute weight loss. This occurs despite normal basal mitochondrial uncoupling protein 1 (UCP1) concentration. In Dio2-/- brown adipocytes, the acute norepinephrine-, CL316,243-, or forskolin-induced increases in lipolysis, UCP1 mRNA, and O2 consumption are all reduced due to impaired cAMP generation. These hypothyroid-like abnormalities are completely reversed by a single injection of T3 14 hours earlier. Recent studies suggest that UCP1 is primarily dependent on thyroid hormone receptor β(TRβ) while the normal sympathetic response of brown adipocytes requires TRα. Intracellularly generated T3 may be required to saturate the TRα, which has an approximately fourfold lower T3-binding affinity than does TRβ. Thus, D2 is an essential component in the thyroid-sympathetic synergism required for thermal homeostasis in small mammals.

Original languageEnglish
Pages (from-to)1379-1385
Number of pages7
JournalJournal of Clinical Investigation
Volume108
Issue number9
DOIs
StatePublished - Dec 13 2001

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Thyroid Hormone Receptors
Iodide Peroxidase
Brown Adipose Tissue
Thermogenesis
Brown Adipocytes
Genes
Shivering
Lipolysis
Triiodothyronine
Colforsin
Weight Loss
Mammals
Norepinephrine
Thyroid Gland
Homeostasis
Hot Temperature
Messenger RNA
Injections
Uncoupling Protein 1

ASJC Scopus subject areas

  • Medicine(all)

Cite this

De Jesus, L. A., Carvalho, S. D., Ribeiro, M. O., Schneider, M., Kim, S. W., Harney, J. W., ... Bianco, A. C. (2001). The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. Journal of Clinical Investigation, 108(9), 1379-1385. https://doi.org/10.1172/JCI200113803

The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. / De Jesus, Lucia A.; Carvalho, Suzy D.; Ribeiro, Mirian O.; Schneider, Mark; Kim, Sung Woo; Harney, John W.; Larsen, P. Reed; Bianco, Antonio C.

In: Journal of Clinical Investigation, Vol. 108, No. 9, 13.12.2001, p. 1379-1385.

Research output: Contribution to journalArticle

De Jesus, LA, Carvalho, SD, Ribeiro, MO, Schneider, M, Kim, SW, Harney, JW, Larsen, PR & Bianco, AC 2001, 'The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue', Journal of Clinical Investigation, vol. 108, no. 9, pp. 1379-1385. https://doi.org/10.1172/JCI200113803
De Jesus, Lucia A. ; Carvalho, Suzy D. ; Ribeiro, Mirian O. ; Schneider, Mark ; Kim, Sung Woo ; Harney, John W. ; Larsen, P. Reed ; Bianco, Antonio C. / The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 9. pp. 1379-1385.
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