Caudal fourth ventricular administration of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside regulates glucose and counterregulatory hormone profiles, dorsal vagal complex metabolosensory neuron function, and hypothalamic fos expression
Caudal fourth ventricular administration of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside regulates glucose and counterregulatory hormone profiles, dorsal vagal complex metabolosensory neuron function, and hypothalamic fos expression
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DOI：
10.1002/jnr.23230
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发表时间：
2013-09-01
影响因子：
4.2
通讯作者：
Briski, Karen P.
中科院分区：
文献类型：
--
作者：
Ibrahim, Baher A.;Tamrakar, Pratistha;Briski, Karen P.
本研究探讨了雌激素控制后脑AMP激活蛋白激酶（AMPK）活性和血糖调节，反调节激素分泌和下丘脑神经细胞转录状态的假设。将AMPK激活剂5-氨基咪唑-4-甲酰胺-核苷（AICAR）在尾侧第四脑室（CV 4）给药后，从苯甲酸雌二醇（E）或油（O）植入的卵巢切除雌性大鼠中激光显微切割背侧迷走复合体A2去甲肾上腺素能神经元，用于Western印迹分析。E先进AICAR诱导的A2磷酸化AMPK（pAMPK）表达和血糖水平的增加，并需要增强Fos，雌激素受体（ER），单羧酸转运蛋白-2，A2神经元和葡萄糖转运蛋白-3蛋白的皮质酮分泌增强这种治疗模式。CV 4 AICAR还导致下丘脑代谢结构（包括室旁核、腹内侧核和弓状核）Fos免疫标记的位点特异性修饰。目前的研究表明，雌激素调节AMPK激活的尾部后脑A2去甲肾上腺素能神经元在药理学复制的能量短缺，在这方面的大脑，这个传感器是参与神经调节的葡萄糖，部分，通过控制皮质酮分泌。这些数据提供了独特的证据表明，A2神经元表达ER和蛋白，AMPK上调细胞的敏感性，ER介导的信号在模拟能量不足。结果还表明，在这些条件下，雌激素促进这些细胞对葡萄糖和乳酸的摄取。后脑AMPK和下丘脑神经细胞基因组激活之间的相关性的证据提供了新的证据，这个后脑传感器和高阶代谢脑位点之间的功能连接，同时证明了雌激素在这种相互作用的调节作用。(c)2013 Wiley Periodicals，Inc.
This study investigated the hypothesis that estrogen controls hindbrain AMP-activated protein kinase (AMPK) activity and regulation of blood glucose, counterregulatory hormone secretion, and hypothalamic nerve cell transcriptional status. Dorsal vagal complex A2 noradrenergic neurons were laser microdissected from estradiol benzoate (E)- or oil (O)-implanted ovariectomized female rats after caudal fourth ventricular (CV4) delivery of the AMPK activator 5-aminoimidazole-4-carboxamide-riboside (AICAR), for Western blot analysis. E advanced AICAR-induced increases in A2 phospho-AMPK (pAMPK) expression and in blood glucose levels and was required for augmentation of Fos, estrogen receptor- (ER), monocarboxylate transporter-2, and glucose transporter-3 protein in A2 neurons and enhancement of corticosterone secretion by this treatment paradigm. CV4 AICAR also resulted in site-specific modifications in Fos immunolabeling of hypothalamic metabolic structures, including the paraventricular, ventromedial, and arcuate nuclei. The current studies demonstrate that estrogen regulates AMPK activation in caudal hindbrain A2 noradrenergic neurons during pharmacological replication of energy shortage in this area of the brain, and that this sensor is involved in neural regulation of glucostasis, in part, through control of corticosterone secretion. The data provide unique evidence that A2 neurons express both ER and - proteins and that AMPK upregulates cellular sensitivity to ER-mediated signaling during simulated energy insufficiency. The results also imply that estrogen promotes glucose and lactate uptake by these cells under those conditions. Evidence for correlation between hindbrain AMPK and hypothalamic nerve cell genomic activation provides novel proof for functional connectivity between this hindbrain sensor and higher order metabolic brain loci while demonstrating a modulatory role for estrogen in this interaction. (c) 2013 Wiley Periodicals, Inc.