Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene
Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene
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DOI：
10.1152/ajpregu.00393.2012
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发表时间：
2012-12-01
影响因子：
2.8
通讯作者：
Matsumoto, Kozo
中科院分区：
文献类型：
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作者：
Blevins, James E.;Moralejo, Daniel H.;Matsumoto, Kozo
blvins JE, Moralejo DH, Wolden-Hanson TH, Thatcher BS, Ho JM, Kaiyala KJ, Matsumoto K.缺乏胆囊收缩素-1受体基因的Fischer 344大鼠的活动和能量消耗改变。[J] .物理学报，2016,32(1):481 - 481。首次发表于2012年10月31日；doi: 10.1152 / ajpregu.00393.2012。-CCK被假设通过作用于迷走神经传入神经元的CCK1受体（CCK1R）来抑制食物的大小，这些神经元支配胃肠道并投射到后脑。早期的研究表明，肥胖的大冢龙-埃文斯德岛脂肪（OLETF）大鼠携带CCK1R的自发零突变，存在贪食和肥胖。最近的研究表明，具有Fischer 344背景的Cck1r -null基因（Cck1r(-/-)）的大鼠是瘦的和正常食的。在本研究中，对该大鼠菌株的代谢表型进行了进一步的表征。正如预期的那样，CCK1R拮抗剂devazepide未能刺激CCK1R（-/-）大鼠的食物摄入。Cck1r（+/+）大鼠和Cck1r（-/-）大鼠在维持高脂肪饮食时，与低脂对照组相比，都发生了饮食性肥胖（DIO）。Cck1r（-/-）大鼠在黑暗周期比对照组吃得多，在光明周期比对照组吃得少。这些影响伴随着暗循环期间食物摄入量、总自发活动和能量消耗的增加，以及光循环期间呼吸商的明显减少。为了评估对厌氧性因素的反应性增强是否有助于瘦表型，我们研究了黑素素II （MTII）对食物摄入和体重的影响。我们发现Cck1r（-/-）大鼠在中枢和外周给药后，MTII抑制食物摄入和体重的作用增强。这些结果表明，瘦表型可能是由总自发活动和能量消耗的增加所驱动的。
Blevins JE, Moralejo DH, Wolden-Hanson TH, Thatcher BS, Ho JM, Kaiyala KJ, Matsumoto K. Alterations in activity and energy expenditure contribute to lean phenotype in Fischer 344 rats lacking the cholecystokinin-1 receptor gene. Am J Physiol Regul Integr Comp Physiol 303: R1231-R1240, 2012. First published October 31, 2012; doi:10.1152/ajpregu.00393.2012.-CCK is hypothesized to inhibit meal size by acting at CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. Earlier studies have shown that obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic and obese. Recent findings show that rats with CCK1R-null gene on a Fischer 344 background (Cck1r(-/-)) are lean and normophagic. In this study, the metabolic phenotype of this rat strain was further characterized. As expected, the CCK1R antagonist, devazepide, failed to stimulate food intake in the Cck1r(-/-) rats. Both Cck1r(+/+) and Cck1r(-/-) rats became diet-induced obese (DIO) when maintained on a high-fat diet relative to chow-fed controls. Cck1r(-/-) rats consumed larger meals than controls during the dark cycle and smaller meals during the light cycle. These effects were accompanied by increased food intake, total spontaneous activity, and energy expenditure during the dark cycle and an apparent reduction in respiratory quotient during the light cycle. To assess whether enhanced responsiveness to anorexigenic factors may contribute to the lean phenotype, we examined the effects of melanotan II (MTII) on food intake and body weight. We found an enhanced effect of MTII in Cck1r(-/-) rats to suppress food intake and body weight following both central and peripheral administration. These results suggest that the lean phenotype is potentially driven by increases in total spontaneous activity and energy expenditure.