Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, 710061, China.
Physiol Behav. 2012 Jan 18;105(2):234-41. doi: 10.1016/j.physbeh.2011.08.007. Epub 2011 Aug 17.
A role for dorsomedial hypothalamus (DMH) cholecystokinin (CCK) signaling in feeding control has been proposed. Administration of CCK into the DMH reduces food intake and OLETF rats lacking CCK1 receptors (CCK1R) become hyperphagic and obese. We hypothesized that site specific replenishment of CCK1R in the DMH of OLETF rats would attenuate aspects of their feeding deficits. Recombinant vectors of adeno-associated viral (AAV)-mediated expression of CCK1R (AAVCCK1R) were bilaterally delivered into the DMH of OLETF. OLETF rats with AAVCCK1R injections demonstrated a 65% replenishment of Cck1r mRNA expression in the DMH relative to lean LETO control rats. Although this level of replenishment did not significantly affect overall food intake or body weight through 14 weeks following viral injections, meal patterns were partially normalized in OLETF rats receiving AAVCCK1R with a significant decrease in dark cycle meal size and a small but significant decrease in daily food intake in the meal analysis chambers. Importantly, the elevation in blood glucose level of OLETF rats was attenuated by the AAVCCK1R injections (p=0.03), suggesting a role for DMH CCK signaling in glucose homeostasis. In support of this role, administration of CCK into the DMH of intact rats enhanced glucose tolerance, as this occurred through activation of CCK1R but not CCK2R signaling. In conclusion, partial replenishment of CCK1R in the DMH of OLETF rats, although insufficient for altering overall food intake and body weight, normalizes meal pattern changes and reduces blood glucose levels. Our study also shows a novel role of DMH CCK signaling in glucose homeostasis.
已经提出了背内侧下丘脑（DMH）胆囊收缩素（CCK）信号在进食控制中的作用。CCK 被注入 DMH 会减少食物摄入，而缺乏 CCK1 受体（CCK1R）的 OLETF 大鼠则会过度进食和肥胖。我们假设在 OLETF 大鼠的 DMH 中特异性补充 CCK1R 会减轻它们摄食缺陷的某些方面。CCK1R 的腺相关病毒（AAV）介导的表达重组载体（AAVCCK1R）被双侧递送至 OLETF 的 DMH。与 lean LETO 对照大鼠相比，接受 AAVCCK1R 注射的 OLETF 大鼠的 DMH 中 Cck1r mRNA 表达得到了 65%的补充。尽管这种补充水平在病毒注射后 14 周内没有显著影响总体食物摄入量或体重，但在接受 AAVCCK1R 注射的 OLETF 大鼠中，进食模式部分恢复正常，夜间进食量明显减少，在进食分析室中的每日食物摄入量略有减少。重要的是，AAVCCK1R 注射减轻了 OLETF 大鼠的血糖水平升高（p=0.03），表明 DMH CCK 信号在葡萄糖稳态中发挥作用。支持这一作用，CCK 被注入到完整大鼠的 DMH 中会增强葡萄糖耐量，因为这是通过激活 CCK1R 而不是 CCK2R 信号发生的。总之，尽管不足以改变总体食物摄入和体重，但在 OLETF 大鼠的 DMH 中部分补充 CCK1R 可使进食模式变化正常化并降低血糖水平。我们的研究还表明 DMH CCK 信号在葡萄糖稳态中的新作用。
