The effects of the beta3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression

Biochem Biophys Res Commun. 1998 Nov 18;252(2):450-4. doi: 10.1006/bbrc.1998.9667.


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 beta3-adrenoceptor (beta3-AR) agonist BRL 35135, on beta3-AR and UCP mRNA levels in tissues from lean and obese (fa/fa) Zucker rats. beta3-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 beta3-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.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adrenergic beta-Agonists / pharmacology*
  • Animals
  • Base Sequence
  • Body Temperature Regulation / drug effects
  • Carrier Proteins / genetics*
  • DNA Primers / genetics
  • Gene Expression / drug effects
  • Ion Channels
  • Membrane Proteins / genetics*
  • Membrane Transport Proteins*
  • Mitochondrial Proteins*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Obesity / genetics
  • Obesity / metabolism
  • Phenethylamines / pharmacology*
  • Polymerase Chain Reaction
  • Proteins / genetics
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Zucker
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3


  • Adrenergic beta-Agonists
  • Carrier Proteins
  • DNA Primers
  • Ion Channels
  • Membrane Proteins
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • Phenethylamines
  • Proteins
  • RNA, Messenger
  • Ucp1 protein, rat
  • Ucp2 protein, rat
  • Ucp3 protein, rat
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3
  • BRL 35135