beta 3-adrenergic receptors on white and brown adipocytes mediate beta 3-selective agonist-induced effects on energy expenditure, insulin secretion, and food intake - A study using transgenic and gene knockout mice
beta 3-adrenergic receptors on white and brown adipocytes mediate beta 3-selective agonist-induced effects on energy expenditure, insulin secretion, and food intake - A study using transgenic and gene knockout mice
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DOI：
10.1074/jbc.272.28.17686
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发表时间：
1997-07-11
影响因子：
4.8
通讯作者：
Lowell, BB
中科院分区：
文献类型：
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作者：
Grujic, D;Susulic, VS;Lowell, BB
β 3肾上腺素能受体（β，7-AR）主要在白色和棕色脂肪细胞上表达，并且用CL 316，243（一种有效且高选择性的β 3-AR激动剂）对小鼠进行急性治疗产生能量消耗的a倍增加、胰岛素水平的50-100倍增加和食物摄入的40-50%减少。我们产生了缺乏功能性β 3-AR的基因敲除小鼠，并证明这些反应中的每一种都是由β 3-AR专门介导的。然而，负责产生这些动作的组织部位是未知的。在本研究中，创建了基因工程小鼠，其中β 3-AR仅在白色和棕色脂肪细胞中表达（WAT+ BAT-小鼠），或仅在棕色脂肪细胞中表达（BAT-小鼠）。这是通过将组织特异性β 3-AR转基因构建体注射到β 3-AR敲除等位基因纯合的小鼠合子中来实现的。然后用CL急性处理对照、敲除、WAT+BAT和BAT-小鼠，并评估对各种参数的影响。如先前观察到的，CL的所有影响在缺乏β 3-AR的基因敲除小鼠中完全不存在。通过在白色和棕色脂肪细胞（WAT+ BAT小鼠）中转基因重新表达β 3-AR，完全缓解了对O-2消耗、胰岛素分泌和食物摄入的影响，这表明这些反应中的每一种都是由β 3-AR介导的。在白色和/或棕色脂肪细胞中，并且不需要其他组织部位的β 3-AR。重要的是，仅在棕色脂肪细胞（BAT-小鼠）中β 3-AR的转基因再表达未能以任何方式挽救CL介导的对胰岛素水平和食物摄入的影响，并且仅最低限度地恢复对氧消耗的影响，这表明对胰岛素分泌和食物摄入的任何影响以及对氧消耗的完全刺激需要在白色脂肪细胞中存在β 3-AR。β 3-AR的机制。白色脂肪细胞的激动剂刺激产生这些反应是未知的，但可能涉及以前不知道的影响这些过程的新介质。
beta 3-Adrenergic receptors (beta,7-ARs) are expressed predominantly on white and brown adipocytes, and acute treatment of mice with CL 316,243, a potent and highly selective beta 3-AR agonist, produces a a-fold increase in energy expenditure, a 50-100-fold increase in insulin levels, and a 40-50% reduction in food intake, Recently, we generated gene knockout mice lacking functional beta 3-ARs and demonstrated that each of these responses were mediated exclusively by beta 3-ARs. However, the tissue site responsible for producing these actions is unknown. In the present study, genetically engineered mice were created in which beta 3-ARs are expressed exclusively ill white and brown adipocytes (WAT+BAT-mice), or in brown adipocytes only (BAT-mice). This was accomplished by injecting tissue-specific beta 3-AR transgenic constructs into mouse zygotes homozygous for the beta 3-AR knockout allele. Control, knockout, WAT+BAT, and BAT-mice were then treated acutely with CL, and the effects on various parameters were assessed, As previously observed, all effects of CL were completely absent in gene knockout mice lacking beta 3-ARs. The effects on O-2 consumption, insulin secretion, and food intake were completely rescued with transgenic re-expression of beta 3-ARs in white and brown adipocytes (WAT+BAT-mice), demonstrating that each of these responses is mediated exclusively by beta 3-Ars in white and/or brown adipocytes, and that beta 3-ARs in other tissue sites were not required. Importantly, transgenic re-expression of beta 3-Ars in brown adipocytes only (BAT-mice) failed to rescue, in any way, CL-mediated effects on insulin levels and food intake and only minimally restored effects on oxygen consumption, indicating that any effect on insulin secretion and food intake, and a full stimulation of oxygen consumption required the presence of beta 3-ARs in white adipocytes. The mechanisms by which beta 3-AR. agonist stimulation of white adipocytes produces these responses are unknown but may involve novel mediators not previously known to effect: these processes.