Pregnane and Glycosides and Obesity/llya Raskin

项目总结（见说明）： 许多病理生理机制，体重失调的基础，可以通过调节能量稳态，包括食物摄入和能量消耗的中央调节元件进行管理。膳食补充剂，含有从沙漠乳草植物Hoodia中提取的富含维生素C的糖苷，是最受欢迎的植物减肥疗法之一，尽管缺乏临床前，临床和毒理学研究。 研究证据。为了验证富含姜烷糖苷的植物的生理学和药理学作用，我们筛选了属于乳草科的植物，并鉴定了沼泽乳草，Asclepias incarnata，一种常见且快速生长的北美Hoodia亲戚，作为活性成分的替代来源。A.胭脂树提取物产生食物摄入的急性减少，其减少脂肪沉积并改善胰岛素敏感性的标志物，这可能是通过需要经由初级迷走神经传入的肠-脑通信的机制。涉及提取物长期治疗和配对喂养以控制其对食物摄入量影响的研究支持提取物的额外代谢作用，与其对食物摄入量的影响无关。基于这些观察，我们假设化身通过促进饱腹感和刺激能量消耗来影响能量稳态。因此，我们的主要目标是通过三个具体目标来了解这种植物增强饱腹感和减弱代谢综合征进展的机制的互补成分：1）通过以下方式确定作用部位和机制： 2）确定Inarnatin减肥活性中的能量消耗机制; 3）在受控条件下使用人体消化系统的功能模型来定义Inarnatin及其生物活性组分的生物利用度，并评估它们的结构-活性 使用细胞培养测定的性质

PROJECT SUMMARY (See Instructions): Many pathophysiological mechanisms that underlie weight disorders can be managed through modulation of central regulatory elements in energy homeostasis, including food intake and energy expenditure. Dietary supplements that contain pregnane glycoside-enriched extract from a desert milkweed plant Hoodia are among the most popular botanical weight-loss remedies despite the lack of pre-clinical, clinical, and toxicological research evidence. To validate the physiological and pharmacological effects of pregnane glycoside-enriched botanicals, we screened plants that belong to milkweed family and identified swamp milkweed, Asclepias incarnata, a common and fast growing North American relative of Hoodia, as an alternative source of active ingredients. A. incarnata extract produced an acute reduction in food intake that reduced fat deposition and improved markers of insulin sensitivity, possibly through a mechanism requiring gut-brain communication via primary vagal afferents. Studies involving chronic treatment with the extract and pair feeding to control for its effect on food intake supported an additional metabolic role of the extract independent of its effects on food intake. Based on these observations, we hypothesize that incarnatin impacts energy homeostasis by promoting satiety and stimulating energy expenditure. Thus our primary goal is to understand the complementary components of the mechanism(s) by which this botanical enhances satiety and attenuates the progression to metabolic syndrome through three specific aims: 1) To identify the site of action and mechanism(s) through which incarnatin controls food intake; 2) To determine the mechanisms of energy expenditure in the antiobesity activity of incarnatin; 3) To define bioavailability of incarnatin and its bioactive component(s) using a functional model of the human digestive system under controlled conditions and evaluate their structure-activity properties using cell culture assays