CCK Response Deficiency in Synphilin-1 Transgenic Mice.
CCK Response Deficiency in Synphilin-1 Transgenic Mice.
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DOI：
10.1371/journal.pone.0142314
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Moran TH
中科院分区：
文献类型：
--
作者：
Smith WW;Smith M;Yang D;Choi PP;Moghadam A;Li T;Moran TH
此前，我们已经确定了细胞质蛋白 synphilin-1（SP1）在控制小鼠和果蝇的食物摄入和体重方面的新作用。转基因小鼠脑神经元中人 SP1 普遍过度表达，导致食欲亢进，表现为进食量增加。然而，SP1 的这种作用的机制仍有待确定。在这里，我们研究了肠道反馈信号改变在 SP1 对食物摄入影响中的潜在作用。我们检查了外周给予胆细胞分裂素 (CCK)、胰岛淀粉样多肽和胰高血糖素样肽 1 (GLP-1) 受体激动剂 exendin-4 的反应。腹腔注射 CCK 以 1-10 nmol/kg 的剂量显着降低野生型 (WT) 小鼠的葡萄糖摄入量，但未能影响 SP1 转基因小鼠的葡萄糖摄入量。此外，SP1转基因小鼠的背侧迷走神经复合体中CCK诱导的c-Fos表达显着减弱。相比之下，WT 和 SP1 转基因小鼠对胰淀素和 exendin-4 治疗的反应相似。这些研究表明，SP1 会导致 CCK 反应缺陷，这可能导致 synphillin-1 转基因小鼠的进食量增加和整体食欲亢进。
Previously, we have identified a novel role for the cytoplasmic protein, synphilin-1(SP1), in the controls of food intake and body weight in both mice and Drosophila. Ubiquitous overexpression of human SP1 in brain neurons in transgenic mice results in hyperphagia expressed as an increase in meal size. However, the mechanisms underlying this action of SP1 remain to be determined. Here we investigate a potential role for altered gut feedback signaling in the effects of SP1 on food intake. We examined responses to peripheral administration of cholecytokinin (CCK), amylin, and the glucagon like peptide-1 (GLP-1) receptor agonist, exendin-4. Intraperitoneal administration of CCK at doses ranging from 1–10 nmol/kg significantly reduced glucose intake in wild type (WT) mice, but failed to affect intake in SP1 transgenic mice. Moreover, there was a significant attenuation of CCK-induced c-Fos expression in the dorsal vagal complex in SP1 transgenic mice. In contrast, WT and SP1 transgenic mice were similarly responsive to both amylin and exendin-4 treatment. These studies demonstrate that SP1 results in a CCK response deficiency that may contribute to the increased meal size and overall hyperphagia in synphillin-1 transgenic mice.