Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a beta(3)-adrenoceptor agonist
Hypertrophy of brown adipocytes in brown and white adipose tissues and reversal of diet-induced obesity in rats treated with a beta(3)-adrenoceptor agonist
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DOI：
10.1016/s0006-2952(97)00162-7
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发表时间：
1997-07-01
影响因子：
5.8
通讯作者：
HimmsHagen, J
中科院分区：
文献类型：
--
作者：
Ghorbani, M;Claus, TH;HimmsHagen, J
在以前的研究中，我们证明了用一种新的β（3）-肾上腺素能受体激动剂CL 316，243 [（R，R）-5-[2-[[2-（3-氯苯基）-2-羟乙基]-氨基]丙基]-1，3-苯并二恶唑-2，2-二羧酸酯]，促进产热，引起白色脂肪组织（WAT）中多房脂肪细胞的出现，并且延缓了食用高脂肪饮食的幼鼠肥胖症的发展（Himms-Hagen等人，Am J Physiol 266：R1371-R1382，1994）。本研究的目的是确定CL 316，243是否可以逆转大鼠中已建立的饮食诱导的肥胖，并鉴定WAT中出现的多室脂肪细胞。CL 316，243（1 mg/kg/天）输注可减少腹部脂肪，增大的脂肪细胞大小减少，但白色脂肪细胞未丢失。静息代谢率增加了40 - 45%，但食物摄入量没有改变。在腹膜后WAT中出现大量表达解偶联蛋白（UCP）的染色密集的多房棕色脂肪细胞，其中蛋白质含量显著增加。肩胛间棕色脂肪组织（BAT）的UCP含量也明显增加。我们认为CL 316，243诱导的静息代谢率的显著增加发生在BAT和WAT的棕色脂肪细胞中。在WAT中出现的棕色脂肪细胞的起源是不确定的。它们可能是小的棕色前脂肪细胞，表达β 3-肾上腺素受体，但线粒体很少，UCP很少或没有，被β 3-激动剂诱导肥大。(C)1997年爱思唯尔科学公司
In a previous study, we demonstrated that chronic treatment with a new beta(3)-adrenoceptor agonist, CL 316,243 [disodium (R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxazole-2,2- dicarboxylate], promoted thermogenesis, caused the appearance of multilocular adipocytes in white adipose tissue (WAT), and retarded development of obesity in young rats eating a high-fat diet (Himms-Hagen et al., Am J Physiol 266: R1371-R1382, 1994). Objectives of the present study were to find out whether CL 316,243 could reverse established diet-induced obesity in rats and to identify the multilocular adipocytes that appeared in WAT. Infusion of CL 316,243 (1 mg/kg/day) reduced abdominal fat, with a decrease in enlarged adipocyte size but no loss of white adipocytes. The resting metabolic rate increased by 40-45%, but food intake was not altered. Abundant densely stained multilocular brown adipocytes expressing uncoupling protein (UCP) appeared in retroperitoneal WAT, in which a marked increase in protein content occurred. UCP content of interscapular brown adipose tissue (BAT) was also increased markedly. We suggest that the substantial increase in the resting metabolic rate induced by CL 316,243 occurs in brown adipocytes in both BAT and WAT. The origin of the brown adipocytes that appeared in WAT is uncertain. They may have been small brown preadipocytes, expressing beta(3)-adrenoceptors but with few mitochondria and little or no UCP, that were induced to hypertrophy by the beta(3)-agonist. (C) 1997 Elsevier Science Inc.