Dietary Resistant Starch: The role of PYY and GLP-1 in energy balance

膳食抗性淀粉：PYY 和 GLP-1 在能量平衡中的作用

• 批准号: 7282680
• 负责人: Roy Joseph Martin
• 金额: $ 17.84万
• 依托单位: LSU PENNINGTON BIOMEDICAL RESEARCH CTR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7282680
• 关键词: ART protein; Affect; Americas; Animal Feed; Animal Model; Blood; Body fat; Brain; Cessation of life; Desire for food; Diet; Dietary Carbohydrates; Dietary Intervention; Digestion; Disease; Eating; Energy Intake; Equilibrium; Figs - dietary; Food; GLP-I receptor; Gene Expression; Genetic; Homeostasis; Human; Hypothalamic structure; Injection of therapeutic agent; Intake; Knock-out; Knockout Mice; Large Intestine; Lead; Light; Measures; Modeling; Mus; Nerve; Neuropeptides; Nutrient; Obese Mice; Obesity; Operative Surgical Procedures; Overweight; POMC gene; Peptide YY; Peptides; Peripheral; Pharmacologic Substance; Prevention; Pro-Opiomelanocortin; Production; Rattus; Research; Research Personnel; Resistance; Rodent; Role; Satiation; Serum; Signal Transduction; Site; Small Intestines; Starch; Structure of nucleus infundibularis hypothalami; Testing; Therapeutic; Visceral; Visceral Afferent Neuron; afferent nerve; cell motility; concept; design; dietary starch; energy balance; feeding; gastrointestinal; gene interaction; glucagon-like peptide 1; neuropeptide Y; novel; novel strategies; obesity treatment; peptide YY receptor; prevent; proglucagon; programs; receptor; research study; resistance mechanism; response; visceral afferent nerve

DESCRIPTION (provided by applicant): Obesity is the fastest-growing cause of disease and death in America. Seeking diet components that can reduce energy intake becomes an attractive approach to prevent overweight and obesity. Resistant starch is a dietary carbohydrate that resists digestion in the small intestine and is fermented in the large intestine. Our preliminary studies revealed that feeding resistant starch significantly altered energy balance and decreased body fat in rodents. Additionally, resistant starch fed rodents had higher gene expressions for peptide YY (PYY) and proglucagon (a precursor of glucagon-like peptide-1, GLP-1) in the gut, and higher serum levels of PYY and GLP-1 when compared to controls. PYY and GLP-1 are satiety peptides. Administration of either PYY or GLP-1 reduces food intake. Thus, we hypothesize that the decreased body fat is due to increased PYY and/or GLP-1 (PYY/GLP-1) in resistant starch fed animals. The hypothesis will be tested in three specific aims. Specific Aim 1: Determine if PYY and GLP- 1 receptors are required for resistant starch to decrease body fat. This will be achieved by blocking PYY/GLP-1 action through PYY/GLP-1 receptor antagonists or by knocking out of the PYY/GLP-1 receptors. Specific Aim 2: Determine if PYY/GLP-1 decrease body fat via visceral nerves or the brain. The peripheral sites of action for PYY/GLP-1 will be tested by destroying visceral afferent neurons to block signals to the brain. Specific Aim 3: Determine if resistant starch decreases body fat in robust obese animal models. A diet-induced obesity model and a genetic obese model will be used to see if resistant starch can prevent obesity. These experiments will reveal that PYY and GLP-1 are part of the mechanism of resistant starch on reducing body fat. Thus, a simple dietary intervention can increase levels of these peptides and reduce body fat naturally without surgery or pharmaceutical means. The uniqueness of this project is that we will examine nutrient-gene interactions to test a novel concept of diet composition and energy balance. This dietary approach is potentially of great therapeutic importance in the prevention of human obesity.

描述（由申请人提供）：肥胖是美国增长最快的疾病和死亡原因。寻找可以减少能量摄入的饮食成分成为预防超重和肥胖的一种有吸引力的方法。抗性淀粉是一种膳食碳水化合物，可抵抗小肠消化并在大肠中发酵。我们的初步研究表明，喂养抗性淀粉显着改变了啮齿类动物的能量平衡并减少了体脂。此外，与对照组相比，饲喂抗性淀粉的啮齿类动物肠道中肽 YY (PYY) 和胰高血糖素原（胰高血糖素样肽 1，GLP-1 的前体）基因表达较高，血清 PYY 和 GLP-1 水平较高。 PYY 和 GLP-1 是饱腹感肽。服用 PYY 或 GLP-1 会减少食物摄入量。因此，我们假设，抗性淀粉喂养的动物体内脂肪减少是由于 PYY 和/或 GLP-1 (PYY/GLP-1) 增加所致。该假设将在三个具体目标上进行检验。具体目标 1：确定抗性淀粉是否需要 PYY 和 GLP-1 受体来减少体内脂肪。这将通过 PYY/GLP-1 受体拮抗剂阻断 PYY/GLP-1 作用或通过敲除 PYY/GLP-1 受体来实现。具体目标 2：确定 PYY/GLP-1 是否通过内脏神经或大脑减少体脂。 PYY/GLP-1 的外周作用位点将通过破坏内脏传入神经元以阻断至大脑的信号来测试。具体目标 3：确定抗性淀粉是否会降低健壮肥胖动物模型中的体脂。将使用饮食诱发的肥胖模型和遗传性肥胖模型来观察抗性淀粉是否可以预防肥胖。这些实验将揭示PYY和GLP-1是抗性淀粉减少体脂机制的一部分。因此，简单的饮食干预可以增加这些肽的水平并自然地减少体内脂肪，而无需手术或药物手段。该项目的独特之处在于，我们将研究营养-基因相互作用，以测试饮食成分和能量平衡的新概念。这种饮食方法对于预防人类肥胖具有潜在的重要治疗意义。

项目成果

Dietary resistant starch increases hypothalamic POMC expression in rats.

• DOI: 10.1038/oby.2008.483
• 发表时间: 2009-01
• 期刊: OBESITY
• 影响因子: 6.9
• 作者: Shen, Li;Keenan, Michael J.;Martin, Roy J.;Tulley, Richard T.;Raggio, Anne M.;McCutcheon, Kathleen L.;Zhou, Jun
• 通讯作者: Zhou, Jun