The present work measured brown adipose tissue and heart mitochondrial oxygen consumption in hypothyroid rats treated with replacement doses of T3, T4 or T4 plus iopanoic acid and kept at 4°C for 24 h. Heart oxygen consumption in normal, untreated hypothyroid and T4-treated hypothyroid rats was unaffected by cold exposure. In rats treated with T4 plus iopanoic acid, rates of oxygen consumption were normal in those maintained at 4°C as well as in those kept at room temperature, despite serum T3 concentration being significantly decreased. The cold-exposed T3-treated hypothyroid rats showed a marked decrease in oxygen consumption (p<0.02) and α-glycerophosphate dehydrogenase activity, a T3-dependent enzyme. Mitochondrial oxygen consumption in brown fat from normal (p<0.01), T4-(p<0.02) and T4 plus iopanoic acid-treated (p<0.01) rats rose more than twofold in response to cold. In the T3-treated group, oxygen consumption at room temperature was higher (p<0.02) than in any other group at similar temperatures. However, the T3-treated group showed no changes in oxygen consumption in response to cold, perhaps because this group reached the maximal response at room temperature. The untreated and the T3-treated hypothyroid rats (both groups devoid of T4) did not survive at 4°C unless T4 or several-fold replacement amounts of T3 were administered. The data demonstrate the crucial role of T4 in thermogenesis during cold exposure.

We have assessed the relative contribution of the thyroid hormones and noradrenaline (NA) on the calorigenic function of brown adipose tissue (BAT) as indicated by GDP binding and O2 consumption of BAT mitochondria. Male Wistar rats of 200 g body weight were made hypothyroid with 131I. Groups of animals were injected s.c., in divided doses, daily for 10 days, with thyroxine (2 micrograms/100 g body weight) or tri-iodothyronine (T3; 0.3 microgram/100 g body weight). Animals were used 7 days after bilateral or unilateral sympathetic nerve excision of BAT (Sx). Sham-operated rats were used as controls. In normal rats kept at 22 degrees C, GDP binding reached 94 +/- 24 pmol/mg protein; untreated hypothyroid rats had normal binding values whereas the T3-treated group showed an increased binding. Sx induced a sharp fall in the three groups (P < 0.01). After 24-h exposure to 4 degrees C GDP binding increased in normal rats to about 410% (P < 0.01) whereas binding failed to increase in response to cold in the untreated hypothyroid and the T3-treated groups. Sx reduced GDP binding in the three groups significantly (P < 0.01). The consumption of O2 by BAT mitochondria showed similar variations in response to Sx and to cold exposure as did GDP binding. The data indicated that, at room temperature, BAT calorigenesis can function without the thyroid hormones, though not without the catecholamines. The findings in rats exposed to cold showed that the lack of NA was significantly more effective than the lack of thyroid hormones in preventing the BAT hyperactive response. This does not negate an active role for T3 in BAT calorigenesis.

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