Regulation of beta 3-adrenergic receptor mRNA by sympathetic nerves and glucocorticoids in BAT of Zucker obese rats

Abstract

Impaired brown adipose tissue (BAT) thermogenesis in the genetically obese Zucker fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the role of the sympathetic nervous system in modulating the effects of adrenalectomy by studying beta3-adrenergic receptor (AR) and uncoupling protein (UCP) mRNA levels in unilaterally sympathectomized interscapular BAT of lean and obese rats. UCP mRNA levels were increased by adrenalectomy. Sympathetic denervation prevented this adrenalectomy-induced increase in lean rats but not in obese rats. beta 3-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decreased and denervation increased beta 3-AR mRNA in lean rats but the opposite response was observed to both of these manipulations in obese rats. beta 3-AR mRNA and UCP mRNA were negatively correlated in lean rats but positively correlated in obese rats. Norepinephrine increased UCP mRNA levels in denervated BAT of both lean and obese rats and decreased beta 3-AR mRNA in lean rats but not obese rats. These data suggest that the regulation of the beta 3-AR gene in response to sympathetic stimuli and glucocorticoids is abnormal in the obese rat.