The Effects of the β3-Adrenoceptor Agonist BRL 35135 on UCP Isoform mRNA Expression

Abstract

The mitochondrial uncoupling protein UCP-1 uncouples respiration from ATP synthesis in brown adipose tissue (BAT) and thus energy is dissipated as heat. Recently two further isoforms have been identified which may play a similar role in other tissues. We have determined the effects of the rodent-selective β3-adrenoceptor (β3-AR) agonist BRL 35135, on β3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. β3-AR mRNA levels were reduced infa/fawhite (WAT) and brown (BAT) adipose tissue relative to levels in lean littermates. BRL 35135 treatment increased expression levels of β3-AR mRNA in both genotypes. UCP-2 and UCP-3 mRNA levels in BAT, WAT and skeletal muscle were reduced by 2-3 fold in thefa/farats relative to the lean rats. We confirm that BRL 35135 increases BAT UCP-1 mRNA in lean rats, and find that BAT UCP-3 mRNA was reduced 3.2 fold, with no changes in UCP-2 expression. In WAT BRL 35135 increased UCP-2 and UCP-3 expression 2-3 fold in both lean andfa/farats. In lean rats, skeletal muscle UCP-3 mRNA was increased 2.3 fold by BRL 35135 whereas UCP-2 was reduced by 2.2 fold. BRL 35135 had no effects on UCP-2 and UCP-3 expression in skeletal muscle of thefa/farats. Our results demonstrate that mechanisms regulating UCP isoform synthesis infa/farats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.