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.