3,5,3'-Triiodothyronine actively stimulates UCP in brown fat under minimal sympathetic activity.

To investigate the role of type II 5'-deiodinase (5'D-II) in the expression of mitochondrial uncoupling protein (UCP) in brown adipose tissue (BAT), we injected intact male rats with reverse (r) 3,5,3'-triiodothyronine (T3; 100 μg ⋅ 100 g body wt-1 ⋅ day-1), an inhibitor of 5'D-II, for 2-5 days. UCP decreased by ∼20% in rats kept at 28°C and failed to increase during cold exposure (4°C). Next, thyroxine treatment (1-10 μg ⋅ 100 g body wt-1 ⋅ day-1) increased nuclear T3 in rats kept at 28 or 4°C. In these rats, nuclear T3 correlated positively with UCP. In addition, T3 (1-50 μg ⋅ 100 g body wt-1 ⋅ day-1) given to intact rats (5-15 days; 28°C) induced an approximately twofold increase in UCP. In these T3-treated animals, the interscapular BAT thermal response to norepinephrine infusion also correlated positively with T3 dose and UCP content. Treatment with propranolol or reserpine failed to block the T3 induction of UCP (∼1.8- and ∼2.3-fold). The results emphasize the importance of local 5'D-II and reveal an independent role of T3 in the expression of UCP.