Prolonged sleep deprivation of the rat produces a progressive increase in energy expenditure and an eventual decrease in body temperature, which suggests a profound derangement in thermoregulation. Because increased thermogenic activity in brown adipose tissue (BAT) is a likely mechanism mediating the observed increase in energy expenditure, we focused our attention on the effect of total sleep deprivation on BAT type II 5’-deiodinase (5’D-II), since its activation indicates BAT stimulation and is essential for full BAT thermogenic response. Five euthyroid rats were subjected to total (92%) sleep deprivation (euD-rats). Sharing the sleep deprivation apparatus, yoked control rats (euC-rats) received the same degree of physical stimulation as the D-rats, but were only partially (25%) sleep deprived. Additional cage controls (euCC-rats) were housed in the same room. Since during sleep deprivation the animals undergo a reduction in plasma T4concentration and inability to maintain body temperature heralds death, an identical study was performed in five trios of hyperthyroid rats (hyperD-, hyperC-, and hyper CC-rats) given daily ip injections of 15 µg T4/100 g BW, 10 days before and throughout the deprivation period. Experiments were carried out at an ambient temperature of 29 C, close to thermoneutrality for rats. Sleep deprivation in hyperD-rats was maintained until death seemed imminent (9-14 days), and in euD-rats for 12-15 days. Sleep deprivation induced a significant increase in BAT 5’D-II activity in both hyperD- and euD-rats compared with that in euCC-rats (P < 0.01). BAT 5’D-II in euC-rats was also significantly higher than that in euCC-rats (P < 0.05), probably because they were partially sleep deprived. BAT 5’D-II activity in hyperD-rats was increased compared to that in both hyperCand hyperCC-rats (P < 0.05), in which the activity was slightly but not significantly lower than that in euCC-rats. No significant differences were observed in liver and kidney type I 5’-D (5’DI) and in pituitary 5’D-II among euD-rats, euC-rats, and euCCrats. As expected, the hyperthyroid groups (hyperD-rats, hyper- C-rats, and hyperCC-rats) had significantly higher kidney 5’DI and lower pituitary 5’D-II than the euCC-rats. Liver 5’D-I was also significantly increased in the hyperC-rats and hyperCCrats, but not in the hyperD-rats. These observations indicate that total sleep deprivation is associated with a marked increase in BAT 5’D-II activity in both euthyroid and hyperthyroid rats. However, euthyroid rats are more sensitive, since even partial sleep deprivation triggered a response in BAT 5’D-II, whereas total sleep deprivation was required to overcome the suppressive effect of T4-induced thyrotoxicosis on BAT 5’D-II activity. These results indicate that BAT 5’D-II activation in sleep deprivation is not due to hypothyroxinemia and that it results from augmented T4to T3conversion. These results combined with those of previous studies suggest that the increase in energy expenditure during sleep deprivation of rats is at least in part mediated through enhanced BAT thermogenesis induced by thyroid hormone as well as sympathetic stimulation. © 1990 by The Endocrine Society.
