Melatonin enhances leptin expression by rat adipocytes in the presence of insulin
Melatonin enhances leptin expression by rat adipocytes in the presence of insulin
复制标题
DOI：
10.1152/ajpendo.00478.2004
复制
发表时间：
2005-04-01
影响因子：
5.1
通讯作者：
Lima, FB
中科院分区：
文献类型：
--
作者：
Alonso-Vale, MIC;Andreotti, S;Lima, FB
瘦素和褪黑激素在调节体重和能量平衡中发挥着重要作用。这两种激素都表现出昼夜节律，在夜间值会增加。此外，最近在脂肪细胞中描述了褪黑激素受体，瘦素是在脂肪细胞中合成的。在这里，我们研究了褪黑激素及其与胰岛素和地塞米松的相互作用对瘦素表达的影响。将分离的大鼠脂肪细胞单独与褪黑激素 (1 nM) 或与胰岛素 (5 nM) 和/或地塞米松 (7 nM) 组合孵育 6 小时。单独使用褪黑激素或胰岛素不会影响瘦素的表达，但它们一起使瘦素表达增加 120%。地塞米松增加了瘦素 mRNA 含量 (105%)，而褪黑激素并未增强这种效果。同时使用三种激素治疗导致瘦素释放 (250%) 和瘦素 mRNA (100%) 进一步增加。褪黑素可阻止毛喉素诱导的瘦素表达抑制（95%）。此外，褪黑激素刺激瘦素释放的能力（在胰岛素存在的情况下）被百日咳毒素和鲁津吲哚完全阻断。为了进一步了解褪黑激素和胰岛素协同作用的分子基础，对胰岛素信号通路进行了研究。褪黑激素增加了胰岛素诱导的胰岛素受体-β 酪氨酸磷酸化，从而导致下游收敛蛋白 Akt 的丝氨酸磷酸化增加。我们得出的结论是，褪黑激素与胰岛素相互作用并上调胰岛素刺激的瘦素表达。这些效应是由褪黑激素与百日咳毒素敏感的 G(i) 蛋白偶联膜受体（MT1 亚型）结合以及与胰岛素的相互作用引起的，因为胰岛素受体及其汇聚靶点 Akt 是由褪黑激素共同激活的。
Leptin and melatonin play an important role in the regulation of body mass and energy balance. Both hormones show a circadian rhythm, with increasing values at night. In addition, melatonin receptors were recently described in adipocytes, where leptin is synthesized. Here, we investigated the influence of melatonin and its interaction with insulin and dexamethasone on leptin expression. Isolated rat adipocytes were incubated with melatonin (1 nM) alone or in combination with insulin (5 nM) and/or dexamethasone (7 nM) for 6 h. Melatonin or insulin alone did not affect leptin expression, but together they increased it by 120%. Dexamethasone increased leptin mRNA content (105%), and this effect was not enhanced by melatonin. Simultaneous treatment with the three hormones provoked a further increase in leptin release (250%) and leptin mRNA (100%). Melatonin prevented the forskolin-induced inhibition (95%) of leptin expression. In addition, melatonin's ability to stimulate leptin release (in the presence of insulin) was completely blocked by pertussis toxin and luzindole. To gain further insight into the molecular basis of melatonin and insulin synergism, the insulin-signaling pathway was investigated. Melatonin increased the insulin-induced insulin receptor-beta tyrosine phosphorylation, which led to an increased serine phosphorylation of the downstream convergent protein Akt. We concluded that melatonin interacts with insulin and upregulates insulin-stimulated leptin expression. These effects are caused by melatonin binding to the pertussis toxin-sensitive G(i) protein-coupled membrane receptor (MT1 subtype) and the cross talk with insulin, since insulin receptor and its convergent target Akt are coactivated by melatonin.