Melanin-concentrating hormone activates signaling pathways in 3T3-L1 adipocytes
Melanin-concentrating hormone activates signaling pathways in 3T3-L1 adipocytes
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DOI：
10.1152/ajpendo.00161.2002
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发表时间：
2002-09-01
影响因子：
5.1
通讯作者：
Cheatham, B
中科院分区：
文献类型：
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作者：
Bradley, RL;Mansfield, JPR;Cheatham, B
能量稳态由外周信号调节，如瘦素，以及几种厌氧神经肽和厌食神经肽。最近，我们报道了产氧神经肽黑色素浓缩激素（MCH）刺激大鼠脂肪细胞产生瘦素，并且MCH受体（MCH- r1）存在于这些细胞上。在这里，我们发现MCH-R1存在于小鼠3T3-L1脂肪细胞中。用1mum MCH治疗3T3-L1脂肪细胞长达2小时，MCH- r1急剧下调，表明配体诱导的受体下调机制。研究了脂肪细胞中介导MCH-R1作用的潜在信号通路。用1mum MCH处理3T3-L1脂肪细胞，可迅速诱导p44/42 MAPK和pp70 S6激酶活性分别增加3倍和5倍。此外，瞬时转染小鼠瘦素-荧光素酶启动子结构的3T3-L1脂肪细胞在MCH作用后1 h和4 h，瘦素启动子报告基因的表达分别增加了4倍和6倍。此外，mch刺激的瘦素启动子驱动的荧光素酶活性在MAP/ERK激酶抑制剂PD-98059和雷帕霉素（一种抑制pp70 S6激酶激活的抑制剂）存在下降低。这些结果进一步证明了脂肪细胞中MCH信号通路的功能。
Energy homeostasis is regulated by peripheral signals, such as leptin, and by several orexigenic and anorectic neuropeptides. Recently, we reported that the orexigenic neuropeptide melanin-concentrating hormone (MCH) stimulates leptin production by rat adipocytes and that the MCH receptor (MCH-R1) is present on these cells. Here, we show that MCH-R1 is present on murine 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with 1 muM MCH for up to 2 h acutely downregulated MCH-R1, indicating a mechanism of ligand-induced receptor downregulation. Potential signaling pathways mediating MCH-R1 action in adipocytes were investigated. Treatment of 3T3-L1 adipocytes with 1 muM MCH rapidly induced a threefold and a fivefold increase in p44/42 MAPK and pp70 S6 kinase activities, respectively. In addition, 3T3-L1 adipocytes transiently transfected with a murine leptin-luciferase promoter construct showed a fourfold and a sixfold increase in leptin promoter-reporter gene expression at 1 h and 4 h, respectively, in response to MCH. Activity decreased to basal levels at 8 h. Furthermore, MCH-stimulated leptin promoter-driven luciferase activity was diminished in the presence of the MAP/ERK kinase inhibitor PD-98059 and in the presence of rapamycin, an inhibitor of pp70 S6 kinase activation. These results provide further evidence for a functional MCH signaling pathway in adipocytes.