EFFECT OF CL-316,243, A THERMOGENIC BETA-3-AGONIST, ON ENERGY-BALANCE AND BROWN AND WHITE ADIPOSE TISSUES IN RATS
EFFECT OF CL-316,243, A THERMOGENIC BETA-3-AGONIST, ON ENERGY-BALANCE AND BROWN AND WHITE ADIPOSE TISSUES IN RATS
复制标题
DOI：
10.1152/ajpregu.1994.266.4.r1371
复制
发表时间：
1994-04-01
影响因子：
--
通讯作者：
CLAUS, TH
中科院分区：
文献类型：
--
作者：
HIMMSHAGEN, J;CUI, JY;CLAUS, TH
目的是评估一种新的、高选择性的β(3)-肾上腺素能激动剂CL-316,243(CL)(J.D.Bloom，M.D.Dutia，B.D.Johnson，A.Wissner，M.G.Burns，E.Largis，J.A.Dolan，和T.H.Claus，J.Med。化学。35：3081,1992)，关于摄入高脂饮食诱导肥胖的幼鼠的能量平衡和棕色和白色脂肪组织(分别为BAT和WAT)。慢性服用CL可增加体温和24小时能量消耗，主要是通过提高静息代谢率。摄食量没有改变，但屠体脂肪减少了。BAT明显肥厚，解偶联蛋白(UCP)和细胞色素氧化酶含量增加3~4倍。CL处理的大鼠肩关节间蝙蝠的定量免疫电子显微镜显示线粒体较小，每个线粒体的UCP总量没有变化。蝙蝠的四种主要细胞类型(成熟棕色脂肪细胞、前脂肪细胞、间质细胞、内皮细胞)的相对频率没有改变。CL诱导的肥大不同于内源性去甲肾上腺素慢性刺激(冷适应时)所致的肥大，且无增生(DNA含量略有降低)，甲状腺激素(T-4)5‘-脱碘酶活性无升高，UCP浓度无选择性升高。WAT仓库重量较轻，细胞较少(DNA较低。内容物)。一些多房性脂肪细胞出现在这些正常情况下几乎完全单眼的水池(肠系膜、腹股沟、附睾部、腹膜后)。结论：CL不仅促进了BAT线粒体的增殖、产热和总的能量消耗和消瘦，而且在饮食诱导肥胖的早期阶段延缓了Wat增生的发展。
The objective was to assess the effect of a new, highly selective beta(3)-adrenergic agonist, CL-316,243 (CL) (J. D. Bloom, M. D. Dutia, B. D. Johnson, A. Wissner, M. G. Burns, E. E. Largis, J. A. Dolan, and T. H. Claus., J. Med. Chem. 35: 3081, 1992), on energy balance and brown and white adipose tissues (BAT and WAT, respectively) in young rats eating a high-fat diet to induce obesity. Chronic treatment with CL increased body temperature and 24-h energy expenditure, mainly by increasing resting metabolic rate. Food intake was not altered but carcass fat was reduced. Interscapular BAT was markedly hypertrophied, with three- to fourfold increases in the content of uncoupling protein (UCP) and cytochrome oxidase. Quantitative immunoelectron microscopy of interscapular BAT of CL-treated rats showed smaller mitochondria with an unchanged total amount of UCP per mitochondrion. The relative frequency of the four major cell types in BAT (mature brown adipocytes, preadipocytes, interstitial cells, endothelial cells) was not altered. The CL-induced hypertrophy differed from that induced by chronic stimulation by endogenous norepinephrine (as in cold-adaptation) in absence of hyperplasia (there was a slightly reduced DNA content), absence of an increase in the thyroxine (T-4) 5'-deiodinase activity, and absence of a selective increase in UCP concentration. WAT depots weighed less and had fewer cells (lower DNA. content) in the CL-treated rats. Some multilocular adipocytes appeared in these normally almost exclusively unilocular WAT depots (mesenteric, inguinal, epididymal, retroperitoneal). We conclude that CL not only promotes BAT mitochondrial proliferation and thermogenesis and overall energy expenditure and leanness, but also retards the development of WAT hyperplasia during the early stage of diet-induced obesity.