Overduin Joost, Gibbs James, Cummings David E, Reeve Joseph R
Weill Medical College, Cornell University, White Plains, NY 10605, USA; Veterans Administration Puget Sound Health Care System, Office of Research and Development Medical Research Service, Seattle, WA 98108, USA; Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Weill Medical College, Cornell University, White Plains, NY 10605, USA.
Peptides. 2014 Apr;54:71-80. doi: 10.1016/j.peptides.2014.01.008. Epub 2014 Jan 24.
Reduction of food intake by exogenous cholecystokinin (CCK) has been demonstrated primarily for its short molecular form, CCK-8. Mounting evidence, however, implicates CCK-58 as a major physiologically active CCK form, with different neural and exocrine response profiles than CCK-8. In three studies, we compared meal-pattern effects of intraperitoneal injections CCK-8 vs. CCK-58 in undeprived male Sprague-Dawley rats consuming sweetened condensed milk. In study 1, rats (N=10) received CCK-8, CCK-58 (0.45, 0.9, 1.8 and 3.6 nmol/kg) or vehicle before a 4-h test-food presentation. At most doses, both CCK-8 and CCK-58 similarly reduced meal size relative to vehicle. Meal-size reduction prompted a compensatory shortening of the intermeal interval (IMI) after CCK-8, but not after CCK-58, which uniquely increased the satiety ratio (IMI/size of the preceding meal). In the second study, lick patterns were monitored after administration of 0.9 nmol/kg CCK-58, CCK-8 or vehicle. Lick cluster size, lick efficiency and interlick-interval distribution remained unaltered compared to vehicle, implying natural satiation, rather than illness, following both CCK forms. In study 3, threshold satiating doses of the two CCK forms were given at 5 and 30 min after meal termination, respectively. CCK 58, but not CCK-8 increased the intermeal interval and satiety ratio compared to vehicle. In conclusion, while CCK 58 and CCK-8 both stimulate satiation, thereby reducing meal size, CCK-58 consistently exerts a satiety effect, prolonging IMI. Given the physiological prominence of CCK-58, these results suggest that CCK's role in food intake regulation may require re-examination.
外源性胆囊收缩素（CCK）减少食物摄入量的作用主要是通过其短分子形式CCK - 8来实现的。然而，越来越多的证据表明CCK - 58是一种主要的具有生理活性的CCK形式，其神经和外分泌反应谱与CCK - 8不同。在三项研究中，我们比较了腹腔注射CCK - 8与CCK - 58对未禁食的雄性斯普拉格 - 道利大鼠食用甜炼乳时进食模式的影响。在研究1中，大鼠（N = 10）在4小时的测试食物呈现前接受CCK - 8、CCK - 58（0.45、0.9、1.8和3.6 nmol/kg）或赋形剂。在大多数剂量下，与赋形剂相比，CCK - 8和CCK - 58均同样减少了进食量。进食量的减少促使CCK - 8注射后餐间间隔（IMI）出现代偿性缩短，但CCK - 58注射后没有，CCK - 58独特地增加了饱腹感比率（IMI/前一餐的量）。在第二项研究中，在给予0.9 nmol/kg CCK - 58、CCK - 8或赋形剂后监测舔舐模式。与赋形剂相比，舔舐簇大小、舔舐效率和舔舐间隔分布均未改变，这意味着两种CCK形式给药后均是自然饱腹感，而非疾病状态。在研究3中，分别在餐后5分钟和30分钟给予两种CCK形式的阈值饱腹感剂量。与赋形剂相比，CCK - 58增加了餐间间隔和饱腹感比率，但CCK - 8没有。总之，虽然CCK - 58和CCK - 8均刺激饱腹感，从而减少进食量，但CCK - 58持续发挥饱腹感作用，延长餐间间隔。鉴于CCK - 58在生理学上的重要性，这些结果表明CCK在食物摄入调节中的作用可能需要重新审视。
