Abstract
The β3-adrenergic-stimulated thermogenic response in brown adipose tissue (BAT) is impaired in senescent rats, whereas cold-induced thermogenesis is not. To determine if cold exposure can restore β3-adrenergic receptor responsiveness in senescent rats, we examined BAT mitochondrial GDP binding in young and old rats, and UCP mRNA levels in young rats following stimulation by the β3-adrenergic agonist CGP-12177 with and without prior cold exposure. F-344 male rats were maintained at thermoneutrality or exposed to 8°C for 48 hr, followed by a 24-hr period of rewarming before administration of 0.75 mg/kg CGP-12177 or vehicle solution. During the rewarming period, GDP binding remained elevated but UCP mRNA levels with a half-life of 11 hr returned to levels observed in the thermoneutral controls. In young rats, both cold exposure and administration of the β3-adrenergic agonist to thermoneutral controls increased GDP binding 2-fold and UCP mRNA levels 4-fold. However, in cold-exposed young rats, there was no further increase with β3-agonist treatment. In senescent control rats, CGP-12177 did not increase GDP binding, but cold exposure did. However, in cold-exposed old rats, the β3-agonist was now able to increase GDP binding. The induction of UCP mRNA by CGP-12177 was also investigated and found to be 25% less in senescent compared with young rats. These observations indicate that cold exposure restores the impaired β3-adrenergic signal transduction in BAT from senescent rats. One possibility is that cold exposure induces the synthesis of one or more components in the β3-adrenergic pathway in senescent rats. [P.S.E.B.M. 1996, Vol 211]
