Normal feeding and body weight in Fischer 344 rats lacking the cholecystokinin-1 receptor gene.
Normal feeding and body weight in Fischer 344 rats lacking the cholecystokinin-1 receptor gene.
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DOI：
10.1016/j.brainres.2008.12.015
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发表时间：
2009-02-19
期刊：
影响因子：
2.9
通讯作者：
Moralejo DH
中科院分区：
文献类型：
--
作者：
Blevins JE;Overduin J;Fuller JM;Cummings DE;Matsumoto K;Moralejo DH
大量证据表明，胆囊收缩素（CCK）抑制食物摄入的机制之一是通过激活支配胃肠道并投射到后脑的迷走神经传入神经元上的CCK 1受体（CCK 1 R）。OLETF大鼠携带CCK 1 R的自发无效突变，是贪食、肥胖和易患2型糖尿病的。最近，通过将OLETF衍生的CCK 1 R无效基因渗入Fischer 344遗传背景中，我们已经能够产生CCK 1 R缺陷的同源大鼠品系F344.Cck1r−/−，与OLETF大鼠相反，其具有瘦和血糖正常的表型。在本研究中，该大鼠品系的行为和神经生物学表型的特点更充分。正如预期的那样，腹腔注射CCK-8可抑制F344.Cck1r+/+大鼠的食物摄入和Ensure Plus，并在最后区和孤束核的胶状肌、连合和内侧亚区诱导Fos反应，而CCK-8对F344.Cck1r−/−大鼠的食物摄入或Fos诱导没有影响。F344.Cck1r−/−和F344.Cck1r+/+大鼠在体重方面没有差异，并且在Ensure Plus维持2周时显示出相当的体重增加。此外，F344.Cck1r+/+和F344.Cck1r−/−大鼠之间的24小时摄食量和暗相进餐频率或进餐量无差异。正如预期的那样，在对照F344.Cck1r+/+大鼠中，在CCK 1 R处阻断内源性CCK作用可增加摄食量并阻断外周CCK-8的作用。这些结果证实，在F344背景的大鼠中，CCK-1 R介导CCK-8诱导的食物摄入抑制和后脑中Fos激活，并证明选择性基因消融CCK-1 R与改变膳食模式、暴食或适口饮食中体重过度增加无关。
A large body of evidence has demonstrated that one mechanism by which cholecystokinin (CCK) inhibits food intake through activation of CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. OLETF rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic, obese, and predisposed to type 2 diabetes. Recently, by introgressing the OLETF-derived, CCK1R-null gene onto a Fischer 344 genetic background, we have been able to generate a CCK1R-deficient, congenic rat strain, F344.Cck1r−/−, that in contrast to OLETF rats, possesses a lean and normoglycemic phenotype. In the present study, the behavioral and neurobiological phenotype of this rat strain was characterized more fully. As expected, intraperitoneal injections of CCK-8 inhibited intake of chow and Ensure Plus and induced Fos responses in the area postrema and the gelatinosus, commissural and medial subdivisions of the nucleus tractus solitarius of F344.Cck1r+/+ rats, whereas CCK-8 was without effect on food intake or Fos induction in the F344.Cck1r−/− rats. F344.Cck1r−/− and F344.Cck1r+/+ rats did not differ in body weight and showed comparable weight gain when maintained on Ensure Plus for 2 weeks. Also, no difference was found in 24-h food intake, and dark-phase meal frequency or meal size between F344.Cck1r+/+ and F344.Cck1r−/− rats. As expected, blockade of endogenous CCK action at CCK1R increased food intake and blocked the effects of peripheral CCK-8 in control F344.Cck1r+/+ rats. These results confirm that in rats with a F344 background, CCK-1R mediates CCK-8-induced inhibition of food intake and Fos activation in the hindbrain and demonstrate that selective genetic ablation of CCK1R is not associated with altered meal patterns, hyperphagia, or excessive weight gain on a palatable diet.
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DOI：
10.1152/ajpregu.00604.2003
发表时间：
2004-07-01
影响因子：
2.8
作者：
Blevins, JE;Schwartz, MW;Baskin, DG
通讯作者：
Baskin, DG
影响因子：
4.8
作者：
Dakin, CL;Gunn, I;Bloom, SR
通讯作者：
Bloom, SR
影响因子：
2.9
作者：
Emond, M;Ladenheim, EE;Moran, TH
通讯作者：
Moran, TH
DOI：
10.1152/ajpregu.00682.2007
发表时间：
2008-03-01
影响因子：
2.8
作者：
Lo, Chun-Min;Samuelson, Linda C.;Tso, Patrick
通讯作者：
Tso, Patrick
影响因子：
2.9
作者：
Blevins, JE;Hamel, FG;Reidelberger, RD
通讯作者：
Reidelberger, RD