THERMOREGULATION WITH AGE - RESTORATION OF BETA(3)-ADRENERGIC RESPONSIVENESS IN BROWN ADIPOSE-TISSUE BY COLD-EXPOSURE

The beta(3)-adrenergic-stimulated thermogenic response in brown adipos e tissue (BAT) is impaired in senescent rats, whereas cold-induced the rmogenesis is not, To determine if cold exposure can restore beta(3)-a drenergic receptor responsiveness in senescent rats, we examined BAT m itochondrial GDP binding in young and old rats, and UCP mRNA levels in young rats following stimulation by the beta(3)-adrenergic agonist CG P-12177 with and without prior cold exposure. F-344 male rats were mai ntained at thermoneutrality or exposed to 8 degrees C for 48 hr, follo wed by a 24-hr period of rewarming before administration of 0.75 mg/kg CGP-12177 or vehicle solution, During the rewarming period, GDP bindi ng remained elevated but UCP mRNA levels with a half-life of 11 hr ret urned to levels observed in the thermoneutral controls, In young rats, both cold exposure and administration of the beta(3)-adrenergic agoni st to thermoneutral controls increased GDP binding 2-fold and UCP mRNA levels 4-fold, However, in cold-exposed young rats, there was no furt her increase with beta(3)-agonist treatment, In senescent control rats , CGP-12177 did not increase GDP binding, but cold exposure did, Howev er, in cold-exposed old rats, the beta(3)-agonist was now able to incr ease GDP binding, The induction of UCP mRNA by CGP-12177 was also inve stigated and found to be 25% less in senescent compared with young rat s, These observations indicate that cold exposure restores the impaire d beta(3)-adrenergic signal transduction in BAT from senescent rats, O ne possibility is that cold exposure induces the synthesis of one or m ore components in the beta(3)-adrenergic pathway in senescent rats.