Emilsson V, Summers R J, Hamilton S, Liu Y L, Cawthorne M A
Clore Laboratory, University of Buckingham, Hunter Street, Buckingham, MK18 1EG, United Kingdom.
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.
线粒体解偶联蛋白UCP - 1使棕色脂肪组织（BAT）中的呼吸与ATP合成解偶联，从而使能量以热量形式消散。最近又鉴定出另外两种亚型，它们可能在其他组织中发挥类似作用。我们已经确定了啮齿动物选择性β3 - 肾上腺素能受体（β3 - AR）激动剂BRL 35135对瘦型和肥胖（fa/fa） Zucker大鼠组织中β3 - AR和UCP mRNA水平的影响。相对于瘦型同窝仔鼠，fa/fa白色（WAT）和棕色（BAT）脂肪组织中的β3 - AR mRNA水平降低。BRL 35135处理增加了两种基因型中β3 - AR mRNA的表达水平。相对于瘦型大鼠，fa/fa大鼠的BAT、WAT和骨骼肌中的UCP - 2和UCP - 3 mRNA水平降低了2 - 3倍。我们证实BRL 35135增加了瘦型大鼠BAT中的UCP - 1 mRNA，并发现BAT中的UCP - 3 mRNA降低了3.2倍，而UCP - 2表达没有变化。在WAT中，BRL 35135使瘦型和fa/fa大鼠的UCP - 2和UCP - 3表达增加了2 - 3倍。在瘦型大鼠中，BRL 35135使骨骼肌UCP - 3 mRNA增加了2.3倍，而UCP - 2降低了2.2倍。BRL 35135对fa/fa大鼠骨骼肌中的UCP - 2和UCP - 3表达没有影响。我们的结果表明，fa/fa大鼠中调节UCP亚型合成的机制受损，并且WAT可能参与了BRL 35135的产热反应。
