High-performance thermogenesis of brown adipose tissue under hypothermic condition during hibernation in Syrian hamsters.

Hibernation under extreme cold environment needs a preparation period of some length in which most physiological functions are thought to be remodelled in wide range to adapt to hibernation. Brown adipose tissue (BAT) is an indispensable organ to complete the hibernation behavior, particularly in arousing from hibernation of hypothermia. Taking into consideration the restraint of most physiological functions by low body temperature, remodelling before hibernation occurs possibly in BAT function too. A concrete mechanism of the 'preparation' is still unclear, but the molecular-level remodelling of BAT must be performed during the preparation period of hibernation, because most gene expression stops during deep hibernation. The dominant pathway of BAT thermogenesis occurs through the β3-adrenergic receptor. We investigated the role of the β3-adrenergic system in BAT thermogenesis during arousal from hibernation both in vivo and in vitro. Necessary surgical procedures were carried out under isoflurane anesthesia. Stimulation of BAT by CL316,243 significantly facilitated arousal from hibernation and it also induced arousal in deep hibernating animals, while the β3-antagonist SR59230A inhibited arousal from hibernation. Syrian hamsters in the hibernation group (H) contained BAT that was significantly greater in overall mass, total protein, and thermogenic uncoupling protein-1 than BAT from the warm-acclimated group (WA). Although the ability of the β3-agonist CL316,243 to induce BAT thermogenesis at 36°C was no different between H and WA, its maximum ratio over the basal value at 12°C in H was significantly larger than that in WA. Forskolin, adenylyl cyclase activator, stimulation at 12°C produced equivalent BAT responses in these two groups. These results suggest that BAT in hibernating animals has potent thermogenic activity with a highly effective β3-receptor mechanism at lower temperatures. Hence we hypothesized that the high effectiveness of the receptor mechanism may be due to an increase in number of the receptor that possibly occurs during the preparation period. To investigate the hypothesis, we measured β3-receptor mRNA of BAT removed from animals in 4 stages of activity, WA, CA (cold-acclimated), H and IBA (inter-bout arousal, awake phase during hibernation) by using RT-PCR method. Gene expression of the β3-receptor in BAT of hibernating hamster was significantly smaller by about 40% and 60% than that of WA and CA respectively, but was not different from that of IBA. Results showed that the facilitation of BAT function in hibernating animals may be due to remodelling of the messenger pathway between two molecules, β3-receptor and adenylyl cyclase. [ABSTRACT FROM AUTHOR]