Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats
Peripheral versus central effects of glucagon-like peptide-1 receptor agonists on satiety and body weight loss in Zucker obese rats
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DOI：
10.1053/meta.2000.6251
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发表时间：
2000-06-01
影响因子：
9.8
通讯作者：
Blázquez, E
中科院分区：
文献类型：
--
作者：
de Fonseca, FR;Navarro, M;Blázquez, E
本研究探讨了外周与中枢给药胰高血糖素样肽-1（GLP-1）受体激动剂在Wistar和Zucker肥胖大鼠摄食行为调节中的潜在效用。GLP-1（7 - 36）酰胺和毒蜥外泌肽-4的急性中枢（脑室内[ICV]）和外周（皮下[SC]）给药导致摄食量减少至少4小时，毒蜥外泌肽-4的效力远高于GLP-1（7 - 36）酰胺，尤其是外周给药后。Zucker肥胖大鼠（fa/fa）和它们的瘦同窝出生大鼠（Fa/-）均对毒蜥外泌肽-4的急性中枢和外周给药有反应。此外，原位杂交显示，在肥胖和瘦大鼠的几个脑区的GLP-1受体的mRNA的特异性标记。该受体的存在也通过亲和交联试验检测。长期SC施用毒蜥外泌肽-4（每天1次单次注射，在周期的黑暗期开始前1小时）减少了肥胖大鼠的每日食物摄入量并且实际上阻断了体重增加。与之前的研究相比，这些发现表明，两种GLP-1受体激动剂的外周（SC）给药也诱导大鼠的饱腹感和体重减轻，并表明毒蜥外泌肽-4作为治疗糖尿病和/或肥胖症的治疗工具的潜在有用性。Copyright（C）2000 by W.B.桑德斯公司
The present study explores the potential utility of peripheral versus central administration of glucagon-like peptide-1 (GLP-1) receptor agonists in the regulation of feeding behavior in Wistar and Zucker obese rats. Acute central (intracerebroventricular [ICV]) and peripheral (subcutaneous [SC]) administration of both GLP-1 (7-36) amide and exendin-4 resulted in a reduction in food intake for at least 4 hours, exendin-4 being much more potent than GLP-1 (7-36) amide, especially after peripheral administration. Both Zucker obese rats (fa/fa) and their lean littermates (Fa/-) responded to acute central and peripheral administration of exendin-4. Moreover, in situ hybridization revealed specific labeling for the mRNA for GLP-1 receptors in several brain areas of both the obese and lean rats. The presence of this receptor was also detected by affinity cross-linking assays. Long-term SC administration of exendin-4 (1 single injection per day, 1 hour prior to the onset of the dark phase of the cycle) decreased daily food intake and practically blocked weight gain in obese rats. In contrast to previous studies, these findings show that peripheral (SC) administration of both GLP-1 receptor agonists also induces satiety and weight loss in rats, and suggest the potential usefulness of exendin-4 as a therapeutic tool for the treatment of diabetes and/or obesity. Copyright (C) 2000 by W.B. Saunders Company.