UPPER GI TRACT MEDIATION OF THE SATIETY EFFECT OF FATS

摄取脂肪终止的生理机制 在动物和人类中进食是未知的。这项建议是 设计：(1)阐明脂肪诱导的关键刺激因素 餐后饱腹感；(2)确定这种饱腹感的作用部位 刺激；以及(3)检查神经、内分泌或 调节这种饱腹感的神经内分泌机制 SD大鼠的反应。对这种机制的认识 很可能对开发有效的 控制饮食失调的治疗方法，如肥胖和 暴食症。有证据表明，遗传肥胖的动物和 人类对脂肪的饱腹感反应较弱。 因此，这项提案的次要目标是审查 瘦肉型和遗传型脂肪诱导的饱腹感的差异 肥胖的老鼠。 为了确定脂肪诱导的饱腹感所涉及的关键刺激因素， 测试将使用特定的短、中、长和 超长链脂肪。这些物质将被检测其 将它们直接注入胃或胃中会对饱腹感产生影响 正常饲养和假饲养大鼠的十二指肠。地点： 诱导饱腹感的行动将通过测量确定 输液后血液中的甘油三酯水平 脂肪进入肝门静脉或下腔静脉 伪装的和真的喂食的大鼠的胃里的脂肪。 确定神经和/或正常机制的实验 调节那些被确定为最有效的脂肪刺激 还提出了诱导饱足感的方法。全膈下肌 迷走神经切断术，选择性迷走神经切断术，选择性传入和传出 迷走神经切断术和脊髓内脏断流术将用于分析 调节脂肪诱导的饱腹感的神经机制。量测 多肽和选择性多肽拮抗剂的使用 用来评估肠道激素在 调节对那些脂肪最多的饱腹感的反应 有效的刺激，以诱导饱腹感。脂肪对人体的特异性 将评估对各种口服刺激的抑制。 这些脂肪刺激最有效地诱导饱腹感和 那些被发现调节饱腹感反应的机制 在斯普拉格，道利大鼠随后将在相同的 Zucker瘦大鼠和肥胖大鼠的范例。

The physiological mechanism by which ingested fats terminate eating in animals and humans is unknown. This proposal is designed: (1) to elucidate the critical stimuli for fat-induced postprandial satiety; (2) to determine the site of action for such stimuli; and (3) to examine the neural, endocrine or neuroendocrine mechanisms involved in mediating this satiety response in Sprague Dawley rats. Knowlege of such mechanisms are likely to be of major importance for developing effective treatments for the control of eating disorders, such as obesity and bulimia. There is evidence that genetically obese animals and humans are less responsive to the satiating effects of fats. Therefore, a secondary aim of this proposal is to examine differences in fat-induced satiety between lean and genetically obese rats. To determine the critical stimuli involved in fat-induced satiety, tests will be carried out with specific short-, medium-, long-, and very long-chain fats. These substances will be assayed for their effects on satiety by infusing them directly into stomach or duodenum of rats feeding normally or sham feeding. The site of action for inducing satiety will be determined by measuring triglyceride levels in the blood subsequent to infusions, infusing fats into the hepatic-portal vein or the inferior vena cava, on confing fats in the stomach, of sham and real feeding rats. Experiments to determine the neural and/or hormal mechanisms that mediate those fat stimuli determined to be most effective for inducing satiety are also proposed. Total subdiaphragmatic vagotomy, selective vagotomies, selective afferent and efferent vagotomy and spinal visceral disconnection will be used to analyze neural mechanisms mediating fat-induced satiety. Measurement of peptides and the use of selective peptide antagonists will be used to assess the involvement of intestinal hormones in mediating the satiating response to those fats that are the most potent stimuli for inducing satiety. The specificity of fats for inhibition of various oral stimuli will be assessed. Those fat stimuli that are most effective for inducing satiety and those mechanisms that are found to mediate the satiety response in Sprague Dawley rats will be subsequently tested in identical paradigms in lean and obese Zucker rats.