Abstract:
: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. In the present studies, cold exposure increased Dio2(-/-) BAT sympathetic stimulation approximately 10-fold (normal approximately 4-fold); as a result, lipolysis, as well as the mRNA levels of uncoupling protein 1, guanosine monophosphate reductase, and peroxisome proliferator-activated receptor gamma coactivator 1, increased well above the levels detected in the cold-exposed wild-type animals. The sustained Dio2(-/-) BAT adrenergic hyperresponse suppressed the three- to fourfold stimulation of BAT lipogenesis normally seen after 24-48 h in the cold. Pharmacological suppression of lipogenesis with betabeta'-methyl-substituted alpha-omega-dicarboxylic acids of C14-C18 in wild-type animals also impaired adaptive thermogenesis in the BAT. These data constitute the first evidence that reduced adrenergic responsiveness does not limit cold-induced adaptive thermogenesis. Instead, the resulting compensatory hyperadrenergic stimulation prevents the otherwise normal stimulation in BAT lipogenesis during cold exposure, rapidly exhausting the availability of fatty acids. The latter is the preponderant determinant of the impaired adaptive thermogenesis and hypothermia in cold-exposed Dio2(-/-) mice.
journal_name
Diabetesjournal_title
Diabetesauthors
Christoffolete MA,Linardi CC,de Jesus L,Ebina KN,Carvalho SD,Ribeiro MO,Rabelo R,Curcio C,Martins L,Kimura ET,Bianco ACdoi
10.2337/diabetes.53.3.577subject
Has Abstractpub_date
2004-03-01 00:00:00pages
577-84issue
3eissn
0012-1797issn
1939-327Xjournal_volume
53pub_type
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