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 (T-3; 100 mu g . 100 g body wt-l day-l), an inhibitor of 5'D-II, for 2-5 days. UCP decreased by similar to 20% in rats kept at 28 degrees C and failed to increase during cold exposure (4 degrees C). Next, thyroxine treatment (1-10 mu g . 100 g body wt(-1) . day(-1)) increased nuclear T-3 in rats kept at 28 or 4 degrees C. In these rats, nuclear T-3 correlated positively with UCP. In addition, T-3 (1-50 mu g . 100 g body wt(-1) . day(-1)) given to intact rats (5-15 days; 28 degrees C) induced an approximately twofold increase in UCP. In these T-3-treated animals, the interscapular BAT thermal response to norepinephrine infusion also correlated positively with T-3 dose and UCP content. Treatment with propranolol or reserpine failed to block the T-3 induction of UCP (similar to 1.8- and similar to 2.3-fold). The results emphasize the importance of local 5'D-II and reveal an independent role of T-3 in the expression of UCP.