A selective human β3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys
A selective human β3 adrenergic receptor agonist increases metabolic rate in rhesus monkeys
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DOI：
10.1172/jci2496
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发表时间：
1998-06-01
影响因子：
15.9
通讯作者：
MacIntyre, DE
中科院分区：
文献类型：
--
作者：
Fisher, MH;Amend, AM;MacIntyre, DE
脂肪细胞表面β 3肾上腺素能受体的激活导致细胞内cAMP增加并刺激脂解。在棕色脂肪组织中，这用于上调和激活线粒体解偶联蛋白1，其介导解偶联氧化磷酸化的质子传导途径，导致能量消耗的净增加。虽然在非灵长类动物中长期使用β（3）激动剂导致解偶联蛋白1上调和体重减轻，但这种机制与灵长类动物能量代谢的相关性受到质疑，因为灵长类动物的棕色脂肪组织水平要低得多。随着L-755，507（一种对人和恒河猴β 3受体有效的选择性部分激动剂）的发现，我们现在证明恒河猴急性暴露于β 3激动剂可促进脂解和代谢率升高，慢性暴露可增加恒河猴棕色脂肪组织中解偶联蛋白1的表达。这些数据表明β 3受体激动剂在治疗人类肥胖症中的作用。
Activation of beta(3) adrenergic receptors on the surface of adipocytes leads to increases in intracellular cAMP and stimulation of lipolysis. In brown adipose tissue, this serves to upregulate and activate the mitochondrial uncoupling protein 1, which mediates a proton conductance pathway that uncouples oxidative phosphorylation, leading to a net increase in energy expenditure. While chronic treatment with beta(3) agonists in nonprimate species leads to uncoupling protein 1 up-regulation and weight loss, the relevance of this mechanism to energy metabolism in primates, which have much lower levels of brown adipose tissue, has been questioned. With the discovery of L-755,507, a potent and selective partial agonist for both human and rhesus beta(3) receptors, we now demonstrate that acute exposure of rhesus monkeys to a beta(3) agonist elicits lipolysis and metabolic rate elevation, and that chronic exposure increases uncoupling protein 1 expression in rhesus brown adipose tissue. These data suggest a role for beta(3) agonists in the treatment of human obesity.