Pregnane and Glycosides and Obesity/llya Raskin

孕烷和糖苷与肥胖/llya Raskin

• 批准号: 8006959
• 负责人: William T. Cefalu
• 金额: $ 27.22万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8006959
• 关键词: Acute; American; Asclepias; Attenuated; Biological Assay; Biological Availability; Body Weight decreased; Botanicals; Brain; Cell Culture Techniques; Chronic; Clinical; Communication; Deposition; Desire for food; Disease; Eating; Effectiveness; Energy Metabolism; Evaluation; Family; Fatty acid glycerol esters; Glycosides; Goals; Homeostasis; Human; Lead; Metabolic; Metabolic syndrome; Modeling; Molecular; Obesity; Physiological; Plants; Pregnanes; Prevention; Property; Regulatory Element; Relative (related person); Research; Role; Satiation; Site; Source; Structure; Weight; base; dietary supplements; feeding; gastrointestinal system; improved; insulin sensitivity; pre-clinical

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 ofthe 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 ofthe 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 ofthe human digestive system under controlled conditions and evaluate their structure-activity properties using cell culture assays.

体重失调的许多病理生理机制可以通过调节能量稳态的中央调节元件来控制，包括食物摄入和能量消耗。尽管缺乏临床前、临床和毒理学研究证据，但含有来自沙漠马利筋植物仙人掌的富含孕烷糖苷提取物的膳食补充剂是最受欢迎的植物减肥药物之一。为了验证富含孕烷糖苷的植物药的生理和药理作用，我们筛选了属于马利筋科的植物，并鉴定了沼泽马利筋（Asclepias incarnata）作为活性成分的替代来源，这是一种常见且快速生长的北美仙人掌近亲。 A. incarnata 提取物可导致食物摄入量急剧减少，从而减少脂肪沉积并改善胰岛素敏感性标志物，这可能是通过需要通过初级迷走神经传入的肠脑通讯的机制来实现的。涉及提取物长期治疗和配对喂养以控制其对食物摄入影响的研究支持提取物的额外代谢作用，与其对食物摄入的影响无关。基于这些观察，我们假设肉肉素通过促进饱腹感和刺激能量消耗来影响能量稳态。因此，我们的主要目标是了解这种植物药通过三个具体目标增强饱腹感并减缓代谢综合征进展的机制的补充成分：1) 确定作用位点和 incarnatin 控制的机制食物摄入量； 2) 确定incarnatin抗肥胖活性中能量消耗的机制； 3) 在受控条件下使用人体消化系统的功能模型来定义 incarnatin 及其生物活性成分的生物利用度，并使用细胞培养测定评估其结构-活性特性。