The effects of the beta3-adrenoceptor agonist BRL 35135 on UCP isoform mRNA expression.
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.
Emilsson
V
V
Clore Laboratory, University of Buckingham, Hunter Street, Buckingham, MK18 1EG, United Kingdom. valur.emilsson@buck.ac.uk
Summers
R J
RJ
Hamilton
S
S
Liu
Y L
YL
Cawthorne
M A
MA
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001833:Body Temperature Regulation / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D017931:DNA Primers; D007473:Ion Channels; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D010627:Phenethylamines; D011506:Proteins; D012333:RNA, Messenger; C000604373:Ucp1 protein, rat; C000604391:Ucp2 protein, rat; C000604394:Ucp3 protein, rat; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C063157:BRL 35135