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

To study the thermal response of interscapular brown fat (IBF) to norepinephrine (NE), urethan-anesthetized rats (1.2 g/kg ip) mainrained at 28-30°C received a constant venous infusion of NE (0-2 x 10⁴ pmol/min) over a period of 60 min. IBF temperatures (T(IBF)) were recorded with a small thermistor fixed under the IBF pad. Data were plotted against time and expressed as maximal variation (Δt°C). Saline-injected rats showed a decrease in T(IBF) of ~0.6°C. NE infusion increased T(IBF) by a maximum of ~3.0°C at a dose of 10⁴ pmol · min^-1 · 100 g body wt^-1. Surgically thyroidectomized (Tx) rats kept on 0.05% methimazole showed a flat response to NE. Treatment with thyroxine (T₄, 0.8 μg · 100 g^-1 · day^-1) for 2-15 days normalized mitochondrial UCP1 (Western blotting) and IBF thermal response to NE, whereas iopanoic acid (5 mg · 100 g body wt^-1 · day^-1) blocked the effects of T₄. Treatment with 3,5,-triiodothyronine (T₃, 0.6 μg. 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 cafeteria diet for 20 days increased UCP1 levels by ~3.5-fold. Nevertheless, the IBF thermal response was only greater than that of controls when maximal doses of NE (2 x 10⁴ pmol/min and higher) were used. Conclusions: 1) hypothyroidism is associated with a blunted IBF thermal response to NE; 2) two- to fourfold changes in mitochondrial UCP1 concentration are not necessarily translated into heat production during NE infusion.