A role for arcuate cocaine and amphetamine regulated transcript in hyperphagia, thermogenesis, and cold adaptation
A role for arcuate cocaine and amphetamine regulated transcript in hyperphagia, thermogenesis, and cold adaptation
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DOI：
10.1096/fj.02-0805fje
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发表时间：
2003-07-01
期刊：
影响因子：
4.8
通讯作者：
Bloom, S
中科院分区：
文献类型：
--
作者：
Kong, WM;Stanley, S;Bloom, S
我们最近发现，注射下丘脑肽可卡因和安非他明调节转录（CART）到离散的下丘脑核刺激食物摄入。这种刺激在弓状核中特别明显。在这里，我们表明，每天两次弓内注射0.2 nmole CART肽7天与60%的日间食物摄入量增加，对β 3激动剂BRL 35135的产热反应增加85%，棕色脂肪组织UCP-1 mRNA增加60%相关。在一项单独的研究中，使用立体定向靶向基因转移，通过使用聚乙烯亚胺将CART转基因递送到成年大鼠的弓状核。在CART过表达动物中，在自由采食期间以及随后的停药和限食期间，摄食量显著增加。在禁食24小时后，CART过度表达的动物比对照组多减轻了12%的体重。棕色脂肪组织解偶联蛋白-1（UCP-1）mRNA水平（第25天采集）在CART过表达动物中高出80%。最后，通过定量原位杂交，我们发现慢性冷暴露（4 ℃下20天）使弓状核CART mRNA增加了124%。结合CART的食欲和产热效应，这一发现表明弓状核CART在冷适应中的作用。
We have recently shown that injection of the hypothalamic peptide cocaine and amphetamine regulated transcript (CART) into discrete hypothalamic nuclei stimulates food intake. This stimulation was particularly marked in the arcuate nucleus. Here we show that twice daily intra-arcuate injection of 0.2 nmole CART peptide for 7 days was associated with a 60% higher daytime food intake, an 85% higher thermogenic response to the beta3 agonist BRL 35135, and a 60% increase in brown adipose tissue UCP-1 mRNA. In a separate study, using stereotactically targeted gene transfer, a CART transgene was delivered by using polyethylenimine to the arcuate nucleus of adult rats. Food intake was increased significantly during ad libitum feeding and following periods of food withdrawal and food restriction in CART over-expressing animals. CART over-expressing animals lost 12% more weight than controls following a 24-h fast. Brown adipose tissue uncoupling protein-1 (UCP-1) mRNA levels (collected Day 25) were 80% higher in CART over-expressing animals. Finally, by using quantitative in situ hybridization, we found that chronic cold exposure (20 days at 4degreesC) increased arcuate nucleus CART mRNA by 124%. Together with the orexigenic and thermogenic effects of CART, this finding suggests a role for arcuate nucleus CART in cold adaptation.