Head Mitchell A, Jewett David C, Gartner Sarah N, Klockars Anica, Levine Allen S, Olszewski Pawel K
Faculty of Science and Engineering, University of Waikato, Hamilton, New Zealand.
Department of Psychology, University of Wisconsin-Eau Claire, Eau Claire, WI, United States.
Front Endocrinol (Lausanne). 2019 May 15;10:297. doi: 10.3389/fendo.2019.00297. eCollection 2019.
Centrally and peripherally administered oxytocin (OT) decreases food intake and activation of the endogenous OT systems, which is associated with termination of feeding. Evidence gathered thus far points to OT as a facilitator of early satiation, a peptide that reduces the need for a meal that has already begun. It is not known, however, whether OT can diminish a feeling of hunger, thereby decreasing a perceived need to seek calories. Therefore, in the current project, we first confirmed that intraperitoneal (i.p.) OT at 0.3-1 mg/kg reduces food intake in deprived and non-deprived rats. We then used those OT doses in a unique hunger discrimination protocol. First, rats were trained to discriminate between 22- and 2-h food deprivation (hungry vs. sated state) in a two-lever operant procedure. After rats acquired the discrimination, they were food-restricted for 22 h and given i.p. OT before a generalization test session. OT did not decrease 22-h deprivation-appropriate responding to match that following 2-h food deprivation, thus, it did not reduce the perceived level of hunger. In order to better understand the mechanisms behind this ineffectiveness of OT, we used c-Fos immunohistochemistry to determine whether i.p. OT activates a different subset of feeding-related brain sites under 22- vs. 2-h deprivation. We found that in sated animals, OT induces c-Fos changes in a broader network of hypothalamic and brain stem sites compared to those affected in the hungry state. Finally, by employing qPCR analysis, we asked whether food deprivation vs. sated state have an impact on OT receptor expression in the brain stem, a CNS "entry" region for peripheral OT. Fasted animals had significantly lower OT receptor mRNA levels than their -fed counterparts. We conclude that OT does not diminish a feeling of hunger before a start of a meal. Instead OT's anorexigenic properties are manifested once consumption has already begun which is-at least to some extent-driven by changes in brain responsiveness to OT treatment in the hungry vs. fed state. OT should be viewed as a mediator of early satiation rather than as a molecule that diminishes perceived hunger.
中枢和外周给予的催产素（OT）可减少食物摄入量，并降低内源性OT系统的激活，这与进食终止有关。迄今为止收集的证据表明，OT是早期饱腹感的促进因子，是一种能减少对已开始进食需求的肽。然而，尚不清楚OT是否能减轻饥饿感，从而降低对热量的感知需求。因此，在当前项目中，我们首先证实腹腔注射（i.p.）0.3 - 1 mg/kg的OT可减少饥饿和非饥饿大鼠的食物摄入量。然后，我们在一个独特的饥饿辨别实验方案中使用了这些OT剂量。首先，在双杠杆操作性实验程序中，训练大鼠区分22小时和2小时的食物剥夺（饥饿与饱腹状态）。大鼠学会辨别后，对它们进行22小时的食物限制，并在泛化测试阶段前给予腹腔注射OT。OT并没有减少对22小时食物剥夺的适当反应，以使其与2小时食物剥夺后的反应相匹配，因此，它并没有降低感知到的饥饿程度。为了更好地理解OT这种无效性背后的机制，我们使用c-Fos免疫组织化学来确定腹腔注射OT在22小时与2小时食物剥夺情况下是否激活不同的与进食相关的脑区子集。我们发现，与饥饿状态下受影响的脑区相比，在饱腹动物中，OT在下丘脑和脑干部位的更广泛网络中诱导c-Fos变化。最后，通过qPCR分析，我们询问食物剥夺与饱腹状态是否会影响脑干中OT受体的表达，脑干是外周OT进入中枢神经系统的区域。禁食动物的OT受体mRNA水平明显低于进食的对应动物。我们得出结论，OT在进食开始前不会减轻饥饿感。相反，OT的厌食特性在进食已经开始后才表现出来，这至少在一定程度上是由饥饿与进食状态下大脑对OT治疗反应性的变化驱动的。OT应被视为早期饱腹感的调节因子，而不是一种能减轻感知饥饿的分子。
