Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat

To study the thermal response of interscapular brown fat (IBF) to norepinep hrine (NE), urethan-anesthetized rats (1.2 g/kg ip) maintained at 28-30 deg rees C received a constant venous infusion of NE (0-2 X 10(4) pmol/min) ove r a period of 60 min. IBF temperatures (T-IBF) were recorded with a small t hermistor fixed under the IBF pad. Data were plotted against time and expre ssed as maximal variation (Delta t degrees C). Saline-injected rats showed a decrease in T-IBF of similar to 0.6 degrees C. NE infusion increased T-IB F by a maximum of similar to 3.0 degrees C at a dose of 10 pmol . min(-1) . 100 g body wt(-1). Surgically thyroidectomized (Tx) rats kept on 0.05% met himazole showed a flat response to NE. Treatment with thyroxine (T-4, 0.8 m g . 100 g(-1) . day(-1)) for 2-15 days normalized mitochondrial UCP1 (Weste rn blotting) and IBF thermal response to NE, whereas iopanoic acid (5 mg . 100 g body wt (-1) . day (-1)) blocked the effects of T-4. Treatment with 3 ,5,3'-triiodothyronine (T-3, 0.6 mu g . 100 g body wt(-1) . day(-1)) for up to 15 days did not normalize UCP1 levels. However, these animals showed a normal IBF thermal response to NE. Cold exposure for 5 days or feeding a ca feteria diet for 20 days increased UCP1 levels by similar to 3.5-fold. Neve rtheless, the IBF thermal response was only greater than that of controls w hen maximal doses of NE (2 3 10(4) pmol/min and higher) were used. Conclusi ons: 1) hypothyroidism is associated with a blunted IBF thermal response to NE; 2) two- to fourfold changes in mitochondrial UCP1 concentration are no t necessarily translated into heat production during NE infusion.