Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue
Leucine is a direct-acting nutrient signal that regulates protein synthesis in adipose tissue
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DOI：
10.1152/ajpendo.00084.2002
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发表时间：
2002-09-01
影响因子：
5.1
通讯作者：
Vary, TC
中科院分区：
文献类型：
--
作者：
Lynch, CJ;Patson, BJ;Vary, TC
在新鲜分离的大鼠脂肪细胞中，亮氨酸或其类似物正亮氨酸激活哺乳动物雷帕霉素靶蛋白（mTOR）信号通路。这导致核糖体蛋白S6激酶1（S6 K1）和真核起始因子4 E-结合蛋白-1（4 E-BP 1）的磷酸化，这两种蛋白质参与蛋白质合成的起始阶段。本文报道的研究的目的是解决亮氨酸和正亮氨酸对脂肪细胞的这些体外作用是否可以扩展到完整动物和其他组织的问题。为了实现这一点，对禁食（18小时）的雄性Sprague-Dawley大鼠口服含有生理盐水（0.9%NaCl）、碳水化合物混合物（26.2%D-葡萄糖和26.2%蔗糖）、亮氨酸（5.4%）或正亮氨酸（5.4%）的溶液（2.5 ml/100 g体重）。测量脂肪组织的蛋白质合成反应，并与其他组织的蛋白质合成反应进行比较。此外，测量S6 K1和4 E-BP 1磷酸化，以及胰岛素的血浆浓度和组织ATP浓度。亮氨酸的管理刺激蛋白质合成脂肪组织，腓肠肌，肾脏，但不是在肝脏和心脏。正亮氨酸刺激蛋白质的合成，在所有的组织测试，但相反，亮氨酸，不影响血浆胰岛素浓度。碳水化合物餐对任何测试组织中的蛋白质合成没有影响，但引起血浆胰岛素的强烈增加。这些发现为亮氨酸作为直接作用的营养信号刺激脂肪组织以及其他选择组织中的蛋白质合成的作用提供了支持。在脂肪组织中，不同处理条件对蛋白质合成的急性调节的影响与S6 K1和4 E-BP 1磷酸化的变化密切相关;然而，这种相关性并不存在于所有检查的组织中。这一结果表明，亮氨酸或正亮氨酸可以通过一种独立于S6 K1和4 E-BP 1磷酸化的机制，至少在某些组织中急性刺激蛋白质合成。
In freshly isolated rat adipocytes, leucine or its analog norleucine activates the mammalian target of rapamycin (mTOR)-signaling pathway. This results in phosphorylation of the ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), two proteins involved in the initiation phase of protein synthesis. The purpose of the studies reported herein was to address the question of whether or not these in vitro effects of leucine and norleucine on adipocytes could be extended to the intact animal and to other tissues. To accomplish this, food-deprived (18 h) male Sprague-Dawley rats were orally administered solutions (2.5 ml/100 g body wt) containing normal saline (0.9% NaCl), a carbohydrate mixture (26.2% D-glucose and 26.2% sucrose), leucine (5.4%), or norleucine (5.4%). The protein synthetic responses of adipose tissue were measured and compared with those of other tissues. In addition, S6K1 and 4E-BP1 phosphorylation was measured, as was the plasma concentration of insulin and tissue ATP concentrations. Leucine administration stimulated protein synthesis in adipose tissue, gastrocnemius, and kidney but not in liver and heart. Norleucine stimulated protein synthesis in all of the tissues tested but, in contrast to leucine, without affecting plasma insulin concentrations. The carbohydrate meal had no effect on protein synthesis in any tissue tested but elicited a robust increase in plasma insulin. These findings provide support for a role of leucine as a direct-acting nutrient signal for stimulation of protein synthesis in adipose tissue as well as other select tissues. In adipose tissue, the effects of the different treatment conditions on the acute regulation of protein synthesis closely correlated with changes in phosphorylation of S6K1 and 4E-BP1; however, this correlation did not exist in all tissues examined. This result implies that leucine or norleucine may acutely stimulate protein synthesis, at least in some tissues, by a mechanism that is independent of both S6K1 and 4E-BP1 phosphorylation.