Pregnane and Glycosides and Obesity/llya Raskin

孕烷和糖苷与肥胖/llya Raskin

• 批准号: 8543516
• 负责人: William T. Cefalu
• 金额: $ 52.58万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8543516
• 关键词: Acute; Affect; American; Asclepias; Attenuated; Behavioral; Biological; Biological Assay; Biological Availability; Body Weight decreased; Botanicals; Brain; Brain Stem; Cell Culture Techniques; Chronic; Clinical; Collaborations; Communication; Crude Extracts; Deposition; Desire for food; Diet; Disease; Eating; Effectiveness; Energy Metabolism; Epidemic; Evaluation; Family; Fatty acid glycerol esters; Food Energy; Frequencies; Funding; Gastric Emptying; Gastroparesis; Genes; Glycosides; Goals; Homeostasis; Human; Hypothalamic structure; Instruction; Lead; Marketing; Measures; Messenger RNA; Metabolic; Metabolic syndrome; Mitochondria; Modeling; Molecular; Mus; Obesity; Pattern; Peptides; Physiological; Physiological Processes; Plant Roots; Plants; Pregnanes; Prevention; Property; Proteins; Rattus; Regulatory Element; Relative (related person); Research; Research Personnel; Role; Satiation; Signal Transduction; Simulate; Site; Small Intestines; Solutions; Source; Stomach; Structure; Structure-Activity Relationship; System; Testing; Therapeutic Human Experimentation; Tissues; Weight; Work; adiponectin; base; dietary supplements; energy balance; feeding; gastrointestinal; gastrointestinal system; improved; in vivo; insulin sensitivity; milligram; pre-clinical; response; standard measure

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

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