University of Waikato, Hamilton, New Zealand.
Dairy Goat Co-operative (NZ) Ltd, Hamilton, New Zealand.
Appetite. 2018 Jun 1;125:278-286. doi: 10.1016/j.appet.2018.02.015. Epub 2018 Feb 19.
Human and laboratory animal studies suggest that dietary supplementation of a free essential amino acid, l-tryptophan (TRP), reduces food intake. It is unclear whether an acute gastric preload of TRP decreases consumption and whether central mechanisms underlie TRP-driven hypophagia. We examined the effect of TRP administered via intragastric gavage on energy- and palatability-induced feeding in mice. We sought to identify central mechanisms through which TRP suppresses appetite. Effects of TRP on consumption of energy-dense and energy-dilute tastants were established in mice stimulated to eat by energy deprivation or palatability. A conditioned taste aversion (CTA) paradigm was used to assess whether hypophagia is unrelated to sickness. c-Fos immunohistochemistry was employed to detect TRP-induced activation of feeding-related brain sites and of oxytocin (OT) neurons, a crucial component of satiety circuits. Also, expression of OT mRNA was assessed with real-time PCR. The functional importance of OT in mediating TRP-driven hypophagia was substantiated by showing the ability of OT receptor blockade to abolish TRP-induced decrease in feeding. TRP reduced intake of energy-dense standard chow in deprived animals and energy-dense palatable chow in sated mice. Anorexigenic doses of TRP did not cause a CTA. TRP failed to affect intake of palatable yet calorie-dilute or noncaloric solutions (10% sucrose, 4.1% Intralipid or 0.1% saccharin) even for TRP doses that decreased water intake in thirsty mice. Fos analysis revealed that TRP increases activation of several key feeding-related brain areas, especially in the brain stem and hypothalamus. TRP activated hypothalamic OT neurons and increased OT mRNA levels, whereas pretreatment with an OT antagonist abolished TRP-driven hypophagia. We conclude that intragastric TRP decreases food and water intake, and TRP-induced hypophagia is partially mediated via central circuits that encompass OT.
人类和实验动物研究表明，补充游离必需氨基酸色氨酸（TRP）可减少食物摄入。目前尚不清楚 TRP 的急性胃预负荷是否会减少消耗，以及中枢机制是否是 TRP 驱动的食欲减退的基础。我们检查了通过胃内灌胃给予 TRP 对小鼠能量和美味诱导进食的影响。我们试图确定 TRP 抑制食欲的中枢机制。在能量剥夺或美味刺激下进食的小鼠中，确定了 TRP 对能量密集和能量稀释味觉剂消耗的影响。使用条件味觉厌恶（CTA）范式来评估食欲减退是否与疾病无关。采用 c-Fos 免疫组织化学检测 TRP 诱导的与摄食相关的脑区和催产素（OT）神经元的激活，OT 神经元是饱食回路的关键组成部分。还使用实时 PCR 评估 OT mRNA 的表达。通过显示 OT 受体阻断能够消除 TRP 诱导的摄食减少，证实了 OT 在介导 TRP 驱动的摄食减少中的重要作用。TRP 减少了饥饿动物的能量密集标准食物和饱食小鼠的能量密集美味食物的摄入量。厌食剂量的 TRP 不会引起 CTA。TRP 不会影响美味但热量稀释或无热量溶液（10%蔗糖，4.1%Intralipid 或 0.1%糖精）的摄入量，即使是降低口渴小鼠水摄入量的 TRP 剂量也不会影响。Fos 分析表明，TRP 增加了几个关键摄食相关脑区的激活，尤其是在脑干和下丘脑。TRP 激活了下丘脑 OT 神经元并增加了 OT mRNA 水平，而 OT 拮抗剂的预处理则消除了 TRP 驱动的摄食减少。我们得出结论，胃内 TRP 可减少食物和水的摄入，而 TRP 诱导的摄食减少部分是通过包含 OT 的中枢回路介导的。
