The effects of the β3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression

Valur Emilsson, Roger J. Summers, Stephanie Hamilton, Yong Ling Liu, Michael A. Cawthorne

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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 in fa/fa white (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 the fa/fa rats 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 and fa/fa rats. 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 the fa/fa rats. Our results demonstrate that mechanisms regulating UCP isoform synthesis in fa/fa rats are impaired and that WAT could be involved in the thermogenic response of BRL 35135.

Original languageEnglish
Pages (from-to)450-454
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - 18 Nov 1998

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