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甘丙肽样肽 (GALP) 通过第三脑室室周区星形胶质细胞合成前列腺素 E2 促进产热。

Galanin-like peptide (GALP) facilitates thermogenesis via synthesis of prostaglandin E2 by astrocytes in the periventricular zone of the third ventricle.

机构信息

Faculty of Health Care, Kiryu University, Midori City, Gunma, 379-2392, Japan.

出版信息

J Mol Neurosci. 2013 Jul;50(3):443-52. doi: 10.1007/s12031-013-9952-4. Epub 2013 Jan 26.

Abstract

Administration of galanin-like peptide (GALP) leads to a decrease in both total food intake and body weight 24 h after injection, compared to controls. Moreover, GALP induces an increase in core body temperature. To elucidate the mechanism by which GALP exerts its effect on energy homeostasis, urethane-anesthetized rats were intracerebroventricularly injected with GALP or saline, after which oxygen consumption, heart rate, and body temperature were monitored for 4 h. In some cases, animals were also pretreated with the cyclooxygenase (COX) inhibitor, diclofenac, via intracerebroventricular (i.c.v.) or intravenous (i.v.) injection. c-Fos expression in the brain was also examined after injection of GALP, and the levels of COX and prostaglandin E(2) synthetase (PGES) mRNA in primary cultured astrocytes treated with GALP were analyzed by using qPCR. The i.c.v. injection of GALP caused biphasic thermogenesis, an effect which could be blocked by pretreatment with centrally (i.c.v.), but not peripherally (i.v.) administered diclofenac. c-Fos immunoreactivity was observed in astrocytes in the periventricular zone of the third ventricle. GALP treatment also increased COX-2 and cytosolic PGES, but not COX-1, microsomal PGES-1, or microsomal PGES-2 mRNA levels in cultured astrocytes. We, therefore, suggest that GALP elicits thermogenesis via a prostaglandin E(2)-mediated pathway in astrocytes of the central nervous system.

摘要

给予甘丙肽类似肽(GALP)后,与对照组相比,24 小时后总食物摄入量和体重均下降。此外,GALP 可引起核心体温升高。为了阐明 GALP 对能量平衡发挥作用的机制,用 GALP 或生理盐水对乌拉坦麻醉大鼠进行侧脑室注射,然后监测 4 小时的耗氧量、心率和体温。在某些情况下,动物还通过侧脑室(i.c.v.)或静脉内(i.v.)注射预先用环氧化酶(COX)抑制剂双氯芬酸处理。注射 GALP 后还检查了大脑中的 c-Fos 表达,并通过 qPCR 分析了用 GALP 处理的原代培养星形胶质细胞中 COX 和前列腺素 E2 合酶(PGES)mRNA 的水平。GALP 的侧脑室注射引起双相生热作用,该作用可通过中枢(i.c.v.)而非外周(i.v.)给予双氯芬酸预处理而阻断。c-Fos 免疫反应性在第三脑室室周区的星形胶质细胞中观察到。GALP 处理还增加了 COX-2 和胞质 PGES,但未增加 COX-1、微粒体 PGES-1 或微粒体 PGES-2 mRNA 水平在培养的星形胶质细胞中。因此,我们认为 GALP 通过中枢神经系统星形胶质细胞中的前列腺素 E2 介导途径引起生热作用。

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