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

Abstract

have decreased levels of UCP1, the mitochondrial protein that shunts the energy derived from mitochondrial fatty acid oxidation from ATP formation to thermogenesis Physiological replacement of T4, but not T3, rapidly restores adrenergic responsiveness, UCP1 gene expression, and BAT thermogenesis by a mechanism that is blocked by iopanoic acid (IOP). This is explained by the high D2 activity in hypothyroid BAT, which catalyzes the activation of T4 to T3 (5, 11). This compensates for the fall in circulating T4, since administration of only small amount of T4 to hypothyroid rats (only 25% of the daily replacement dose) increases BAT TR occupancy to about 50%, almost exclusively due to locally generated T3 (19).