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

MO Ribeiro, FLAS Lebrun… - American Journal …, 2000 - journals.physiology.org
MO Ribeiro, FLAS Lebrun, MA Christoffolete, M Branco, A Crescenzi, SD Carvalho…
American Journal of Physiology-Endocrinology and Metabolism, 2000journals.physiology.org
To study the thermal response of interscapular brown fat (IBF) to norepinephrine (NE),
urethan-anesthetized rats (1.2 g/kg ip) maintained at 28–30° C received a constant venous
infusion of NE (0–2× 104 pmol/min) over a period of 60 min. IBF temperatures (TIBF) were
recorded with a small thermistor fixed under the IBF pad. Data were plotted against time and
expressed as maximal variation (Δ t° C). Saline-injected rats showed a decrease in TIBF
of∼ 0.6° C. NE infusion increased TIBF by a maximum of∼ 3.0° C at a dose of 104 pmol …
To study the thermal response of interscapular brown fat (IBF) to norepinephrine (NE), urethan-anesthetized rats (1.2 g/kg ip) maintained at 28–30°C received a constant venous infusion of NE (0–2 × 104 pmol/min) over a period of 60 min. IBF temperatures (TIBF) 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 TIBF of ∼0.6°C. NE infusion increased TIBF 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 3,5,3′-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 × 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.
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