Isoproterenol decreases leptin release from rat and human adipose tissue through posttranscriptional mechanisms.
Isoproterenol decreases leptin release from rat and human adipose tissue through posttranscriptional mechanisms.
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异丙肾上腺素通过转录后机制减少大鼠和人类脂肪组织中瘦素的释放。
DOI：
10.1152/ajpendo.00446.2004
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Fried,SusanK
中科院分区：
文献类型：
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作者：
Ricci,MatthewR;Lee,Mi-Jeong;Russell,ColleenD;Wang,Yanxin;Sullivan,Sean;Schneider,StephenH;Brolin,RobertE;Fried,SusanK
在体内和体外研究表明，β-肾上腺素能受体激动剂减少瘦素释放脂肪细胞在短短30分钟。我们的目的是确定是否在瘦素的生物合成或分泌的改变参与短期肾上腺素调节瘦素在人类和大鼠脂肪组织。异丙肾上腺素（Iso）降低非肥胖和肥胖受试者脂肪组织中瘦素释放的程度相似（3小时后分别为-28%和-21%）。放线菌酮蛋白质合成的抑制并没有阻断Iso对人脂肪组织中瘦素释放的影响，这表明Iso效应与瘦素合成无关。ISO也倾向于增加组织瘦素含量在3小时孵育结束时，从所观察到的抑制释放的预期。与翻译后机制一致，Iso处理不影响瘦素mRNA水平或瘦素生物合成的相对速率，直接通过[35 S]蛋氨酸掺入免疫沉淀瘦素进行评估。与人脂肪组织中的这些结果相反，Iso没有降低大鼠脂肪组织的基础瘦素释放。然而，Iso确实通过抑制胰岛素增加瘦素生物合成的能力来减少胰岛素刺激的瘦素释放，而不可检测地影响瘦素mRNA水平。因此，在人类和大鼠中，肾上腺素能调节转录后事件（人类的分泌，大鼠的翻译）可能有助于循环瘦素的快速下降，当交感神经系统被激活时，如在禁食和寒冷暴露期间。此外，大鼠没有提供理想的模型来研究人类细胞瘦素调节的机制。
In vivo and in vitro studies indicate that β-adrenergic receptor agonists decrease leptin release from fat cells in as little as 30 min. Our objective was to determine whether alterations in leptin biosynthesis or secretion were involved in the short-term adrenergic regulation of leptin in human and rat adipose tissue. Isoproterenol (Iso) decreased leptin release from incubated adipose tissue of both nonobese and obese subjects to similar extent (−28 vs. −21% after 3 h). Inhibition of protein synthesis with cycloheximide did not block the effect of Iso on leptin release from human adipose tissue, suggesting that the Iso effect is independent of leptin synthesis. Iso also tended to increase tissue leptin content at the end of the 3-h incubation, as expected from the observed inhibition of release. Consistent with a posttranslational mechanism, Iso treatment did not affect leptin mRNA levels or relative rate of leptin biosynthesis as directly assessed by [35S]methionine incorporation into immunoprecipitable leptin. In contrast to these results in human adipose tissues, Iso did not decrease basal leptin release from rat adipose tissue. However, Iso did decrease insulin-stimulated leptin release by inhibiting the ability of insulin to increase leptin biosynthesis without detectably affecting leptin mRNA levels. Thus, in both human and rat, adrenergic regulation of posttranscriptional events (secretion in humans, translation in rats) may contribute to the rapid decline in circulating leptin that occurs when the sympathetic nervous system is activated, such as during fasting and cold exposure. Furthermore, the rat does not provide an ideal model to study mechanisms of cellular leptin regulation in humans.