REGULATION OF BETA(3)-ADRENERGIC RECEPTOR MESSENGER-RNA BY SYMPATHETIC-NERVES AND GLUCOCORTICOIDS IN BAT OF ZUCKER OBESE RATS

Impaired brown adipose tissue (BAT) thermogenesis in the genetically o bese Zucker fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the role of the sympathetic nervous system in modulati ng the effects of adrenalectomy by studying beta(3)-adrenergic recepto r (AR) and uncoupling protein (UCP) mRNA levels in unilaterally sympat hectomized interscapular BAT of lean and obese rats. UCP mRNA levels w ere increased by adrenalectomy. Sympathetic denervation prevented this adrenalectomy-induced increase in lean rats but not in obese rats. be ta(3)-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decrea sed and denervation increased beta(3)-AR mRNA in lean rats but the opp osite response was observed to both of these manipulations in obese ra ts. beta(3)-AR mRNA and UCP mRNA were negatively correlated in lean ra ts but positively correlated in obese rats. Norepinephrine increased U CP mRNA levels in denervated BAT of both lean and obese rats and decre ased beta 3-AR mRNA in lean rats but not obese rats. These data sugges t that the regulation of the beta(3)-AR gene in response to sympatheti c stimuli and glucocorticoids is abnormal in the obese rat.