Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons.
Adiponectin inhibits KISS1 gene transcription through AMPK and specificity protein-1 in the hypothalamic GT1-7 neurons.
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DOI：
10.1530/joe-12-0054
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发表时间：
2012-08
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影响因子：
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通讯作者：
Jun-ping Wen;Chun-e Liu;Wen-kai Bi;Yanxu Hu;Qingshi Chen;Huibing Huang;Ji-xing Liang;Lian-tao Li;Li-xiang Lin;Gang Chen
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文献类型：
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作者：
Jun-ping Wen;Chun-e Liu;Wen-kai Bi;Yanxu Hu;Qingshi Chen;Huibing Huang;Ji-xing Liang;Lian-tao Li;Li-xiang Lin;Gang Chen
由脂肪组织分泌的脂联素在下丘脑的能量平衡、食物摄取和生殖的调节中起作用。我们以前已经证明，脂联素显着抑制从GT 1 -7下丘脑GNRH神经元细胞的GNRH分泌。在本研究中，我们进一步研究了脂联素对下丘脑KISS 1基因转录的影响，这是GNRH的上游信号。我们发现，球状脂联素（gAd）或AICAR，人工AMPK激活剂，降低KISS 1 mRNA转录和启动子活性。相反，化合物C或AMPKα1-SiRNA对AMPK的抑制增强了KISS 1 mRNA转录和启动子活性。此外，gAd和AICAR抑制特异性蛋白1（SP1）从胞质向核的转位，而化合物C和AMPKα1-siRNA则起相反作用。我们的体内实验表明，与对照组相比，化合物C处理的大鼠中Kiss 1 mRNA的表达被刺激两倍，而gAd或AICAR处理的大鼠中Kiss 1 mRNA的表达降低约60-70%。Sprague道利大鼠弓状核区kisspeptin免疫阳性神经元的数量与不同治疗组动物中Kiss 1 mRNA水平的趋势相同。总之，我们的研究结果提供了第一个证据表明，脂联素减少Kiss 1基因转录在GT 1 -7细胞通过激活AMPK，随后减少SP1的易位。
Adiponectin secreted from adipose tissues plays a role in the regulation of energy homeostasis, food intake, and reproduction in the hypothalamus. We have previously demonstrated that adiponectin significantly inhibited GNRH secretion from GT1-7 hypothalamic GNRH neuron cells. In this study, we further investigated the effect of adiponectin on hypothalamic KISS1 gene transcription, which is the upstream signal of GNRH. We found that globular adiponectin (gAd) or AICAR, an artificial AMPK activator, decreased KISS1 mRNA transcription and promoter activity. Conversely, inhibition of AMPK by Compound C or AMPKα1-SiRNA augmented KISS1 mRNA transcription and promoter activity. Additionally, gAd and AICAR decreased the translocation of specificity protein-1 (SP1) from cytoplasm to nucleus; however, Compound C and AMPKα1-siRNA played an inverse role. Our experiments in vivo demonstrated that the expression of Kiss1 mRNA was stimulated twofold in the Compound C-treated rats and decreased about 60-70% in gAd- or AICAR-treated rats compared with control group. The numbers of kisspeptin immunopositive neurons in the arcuate nucleus region of Sprague Dawley rats mimicked the same trend seen in Kiss1 mRNA levels in animal groups with different treatments. In conclusion, our results provide the first evidence that adiponectin reduces Kiss1 gene transcription in GT1-7 cells through activation of AMPK and subsequently decreased translocation of SP1.