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, cold-exposed 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.
Lucia A. de Jesus, Suzy D. Carvalho, Mirian O. Ribeiro, Mark Schneider, Sung-Woo Kim, John W. Harney, P. Reed Larsen, Antonio C. Bianco
Title and authors | Publication | Year |
---|---|---|
American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models
AC Bianco, G Anderson, D Forrest, VA Dr, B Gereben, BW Kim, PA Kopp, XH Liao, MJ Obregon, R Peeters, S Refetoff, D Sharlin, WS Simonides, RE Weiss, G Williams |
Thyroid | 2013 |
The role of thyroid hormone and brown adipose tissue in energy homoeostasis
AC Bianco, EA McAninch |
The Lancet Diabetes & Endocrinology | 2013 |
Thyroid Hormones and the Metabolic Syndrome
KA Iwen, E Schröder, G Brabant |
European Thyroid Journal | 2013 |
Targeted Deletion of Fibrinogen Like Protein 1 Reveals a Novel Role in Energy Substrate Utilization
V Demchev, G Malana, D Vangala, J Stoll, A Desai, HW Kang, Y Li, H Nayeb-Hashemi, M Niepel, DE Cohen, C Ukomadu |
PloS one | 2013 |
Brown and beige fat: development, function and therapeutic potential
M Harms, P Seale |
Nature Medicine | 2013 |
Assessment of brown adipose tissue function
S Virtue, A Vidal-Puig |
Frontiers in physiology | 2013 |
The deiodinases and the control of intracellular thyroid hormone signaling during cellular differentiation☆
M Dentice, A Marsili, AM Zavacki, PR Larsen, D Salvatore |
Biochimica et Biophysica Acta | 2013 |
Metal Ions in Life Sciences
S Kurokawa, MJ Berry |
Metal ions in life sciences | 2013 |
NAT8L (N-Acetyltransferase 8-Like) Accelerates Lipid Turnover and Increases Energy Expenditure in Brown Adipocytes
AR Pessentheiner, HJ Pelzmann, E Walenta, M Schweiger, LN Groschner, WF Graier, D Kolb, K Uno, T Miyazaki, A Nitta, D Rieder, A Prokesch, JG Bogner-Strauss |
The Journal of biological chemistry | 2013 |
Cardiac Expression of Human Type 2 Iodothyronine Deiodinase Increases Glucose Metabolism and Protects Against Doxorubicin-induced Cardiac Dysfunction in Male Mice
EG Hong, BW Kim, DY Jung, JH Kim, T Yu, WS da Silva, RH Friedline, SD Bianco, SP Seslar, H Wakimoto, CI Berul, KS Russell, KW Lee, PR Larsen, AC Bianco, JK Kim |
Endocrinology | 2013 |