Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspects
Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: Developmental aspects
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DOI：
10.1002/dev.20149
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发表时间：
2006-07-01
影响因子：
2.2
通讯作者：
Bi, Sheng
中科院分区：
文献类型：
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作者：
Moran, Timothy H.;Bi, Sheng
Otsuka Long Evans Tokushima Fatty (OLETF) 大鼠的胆囊收缩素-1 (CCK1) 受体编码基因存在缺失，这种缺失会阻止蛋白质表达，使 OLETF 大鼠成为 CCK1 受体敲除模型。与缺乏 CCK1 受体一致，OLETF 大鼠不会因外源施用 CCK 而减少食物摄入量，并且摄入的食物量比正常食物多。这种餐内反馈信号的缺陷在液体和固体食物中都很明显。新生 OLETF 大鼠在独立摄入测试中表现出类似的差异。摄入量更高，反映在更大的舔行为上。新生 OLETF 大鼠的进食潜伏期也缩短，并且大鼠的初始摄入量更高。成年 OLETF 大鼠食量过多且肥胖。尽管弓形核肽基因表达在 OLETF 大鼠中明显正常，但当通过配对喂养对照 Long Evans Tokushima Otsuka (LETO) 大鼠的摄入量来预防肥胖时，OLETF 大鼠背内侧下丘脑 NPY mRNA 表达显着升高。 NPY 过度表达在肥胖前期幼年 OLETF 大鼠中也很明显，表明这种过度表达在食欲亢进和肥胖中具有因果作用。跑轮运动使 OLETF 大鼠的食物摄入量和体重正常化。当 OLETF 大鼠肥胖时提供运动机会时，效果仅限于运动期间。当年轻的肥胖前 OLETF 大鼠可以使用跑轮时，运动会导致食物摄入量和体重的长期持续减少，并改善血糖调节。运动的这些持久代谢效应可能是运动引起的 DMH NPY mRNA 表达减少继发的。 (c) 2006 年 Wiley 期刊公司
Otsuka Long Evans Tokushima Fatty (OLETF) rats have a deletion in the gene encoding the cholecystokinin-1 (CCK1) receptor This deletion prevents protein expression, making the OLETF rat a CCK1 receptor knockout model. Consistent with the absence of CCK1 receptors, OLETF rats do not reduce their food intake in response to exogenously administered CCK and consume larger than normal meals. This deficit in within-meal feedback signaling is evident in liquid as well as solid meals. Neonatal OLETF rats show similar differences in independent ingestion tests. Intake is higher and is reflected in greater licking behavior Neonatal OLETF rats also have diminished latencies to consume and higher initial ingestion rats. Adult OLETF rats are hyperphagic and obese. Although arcuate nucleus peptide gene expression is apparently normal in OLETF rats, when obesity is prevented through pair-feeding to amounts consumed by control Long Evans Tokushima Otsuka (LETO) rats, dorsomedial hypothalamic NPY mRNA expression is significantly elevated in OLETF rats. NPY overexpression is also evident in preobese, juvenile OLETF rats suggesting a causal role for this overexpression in the hyperphagia and obesity. Running wheel exercise normalizes food intake and body weight in OLETF rats. When access to exercise is provided at a time when OLETF rats are obese, the effects are limited to the period of exercise. When running wheel access is available to younger preobese OLETF rats, exercise results in long lasting reductions in food intake and body weight and improved glucose regulation. These lasting metabolic effects of exercise may be secondary to an exercise induced reduction in DMH NPY mRNA expression. (c) 2006 Wiley Periodicals, Inc.