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American Physiological Society, AJP - Endocrinology and Metabolism, 2(279), p. E314-E322, 2000

DOI: 10.1152/ajpendo.2000.279.2.e314

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

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

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 × 104pmol/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 TIBFof ∼0.6°C. NE infusion increased TIBFby a maximum of ∼3.0°C at a dose of 104pmol · 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 × 104pmol/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.