Disease relevance of Dio2

• 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 [1].
• The latter is the preponderant determinant of the impaired adaptive thermogenesis and hypothermia in cold-exposed Dio2(-/-) mice [2].
• The Dio2 gene encodes the type 2 deiodinase (D2) that activates thyroxine (T4) to 3,3',5-triiodothyronine (T3), the disruption of which (Dio2(-/-)) results in brown adipose tissue (BAT)-specific hypothyroidism in an otherwise euthyroid animal [2].
• Since MeHg has a high affinity for thiol groups, we sought to determine whether MeHg inhibited type II iodothyronine deiodinase (D2) activity, by which prohormone thyroxine (T4) is converted to active thyroid hormone, 3,5,3'-triiodothyronine (T3) in the brain, using NB41A3 mouse neuroblastoma cells [3].

High impact information on Dio2

• In Dio2(-/-) brown adipocytes, the acute norepinephrine-, CL316,243-, or forskolin-induced increases in lipolysis, UCP1 mRNA, and O(2) consumption are all reduced due to impaired cAMP generation [1].
• The sustained Dio2(-/-) BAT adrenergic hyperresponse suppressed the three- to fourfold stimulation of BAT lipogenesis normally seen after 24-48 h in the cold [2].
• We measured Dio1 and Dio2 in kidney, skeletal muscle, heart, brown adipose tissue, and brain, but did not find compensatory up-regulation in these tissues [4].
• The type II iodothyronine deiodinase (D2) catalyzes the 5'-deiodination of thyroxine to yield the biologically active form, 3,3',5,-tri-iodothyronine, and is a member of the selenoproteins [5].
• Biochemical and molecular biological evidence for the presence of type II iodothyronine deiodinase in mouse mammary gland [6].

References