Characterization of mice lacking the gene for cholecystokinin

Characterization of mice lacking the gene for cholecystokinin
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DOI:
10.1152/ajpregu.00682.2007
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发表时间:
2008-03-01
影响因子:
2.8
通讯作者:
Tso, Patrick
Tso, Patrick
中科院分区:
医学3区
文献类型:
--
作者:
Lo, Chun-Min;Samuelson, Linda C.;Tso, Patrick

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CCK作为一种饱腹肽,在进食时对脂质摄食做出反应,并在摄食、探索和记忆活动的调节中发挥核心作用。本研究确定了缺乏CCK基因小鼠的代谢参数、食物摄入、焦虑样行为和认知功能。我们采用无创测量肠道脂肪吸收、定量磁共振成像(QMR)和DietMax系统分别研究了CCK基因敲除(CCK- ko)小鼠的肠道脂肪吸收、身体组成和食物摄入量。此外,通过监测跑轮活动和对这些小鼠进行高架+迷宫和Morris水迷宫测试来评估探索和记忆能力。与野生型(WT)对照相比,CCK-KO小鼠的食物摄取量、脂肪吸收、体重和体重均正常。CCK-KO小鼠在光照期比对照组吃得多,在黑暗期比对照组吃得少。基因型之间的能量消耗没有变化;然而,CCK-KO小鼠表现出更大的脂肪酸氧化。在跑轮试验中,CCK-KO小鼠与WT动物一样活跃。CCK-KO小鼠在高架+迷宫的封闭手臂中花费的时间更长,表明焦虑增加。此外,CCK-KO小鼠在被动回避任务中的表现减弱,Morris水迷宫测试中的空间记忆受损。我们得出结论,CCK参与代谢率,对记忆和探索很重要。CCK密切参与与认知功能和食物摄入调节相关的多个过程。
CCK acts peripherally as a satiating peptide released during meals in response to lipid feeding and centrally functions in the modulation of feeding, exploratory, and memory activities. The present study determined metabolic parameters, food intake, anxiety-like behaviors, and cognitive function in mice lacking the CCK gene. We studied intestinal fat absorption, body composition, and food intake of CCK knockout (CCK-KO) mice by using the noninvasive measurement of intestinal fat absorption along with quantitative magnetic resonance (QMR) imaging and the DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity and conducting elevated plus-maze and Morris water-maze tests with these mice. Compared with wild-type (WT) littermate controls, CCK-KO mice had normal food intake, fat absorption, body weight, and body mass. CCK-KO mice ate more food than control animals during the light period and less food during the dark period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and impaired spatial memory in the Morris water maze test. We conclude that CCK is involved in metabolic rate and is important for memory and exploration. CCK is intimately involved in multiple processes related to cognitive function and food intake regulation.