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: 7146411
• 负责人: Roy Joseph Martin
• 金额: $ 22.05万
• 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 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7146411
• 关键词: adipose tissue; bioenergetics; dietary carbohydrates; dietary constituent; dissection; gastrointestinal hormones; gastrointestinal motility /pressure; hormone inhibitor; hormone receptor; incretin hormone; laboratory mouse; laboratory rat; neuropeptides; neuroregulation; obesity; pathogenic diet; polymerase chain reaction; radioimmunoassay; 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(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个有吸引力的方法。抗性淀粉是一种饮食碳水化合物，在小肠中抵抗消化，在大肠中发酵。我们的初步研究表明，喂食抗性淀粉显著改变了啮齿类动物的能量平衡，降低了体脂。此外，与对照组相比，饲喂抗性淀粉的啮齿动物肠道中肽YY(PYY)和前高血糖素(GLP-1的前体)的基因表达增加，血清中PYY和GLP-1的水平升高。PYY和GLP-1均为饱腹肽。服用PYY或GLP-1均可减少食物摄入量。因此，我们假设，体内脂肪的减少是由于抗性淀粉喂养的动物体内PYY和/或GLP-1(PYY/GLP-1)增加所致。这一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受体来降低体内脂肪。这将通过PYY/GLP-1受体拮抗剂或通过敲除PYY/GLP-1受体来阻断PYY/GLP-1的作用。具体目标2：确定PYY/GLP-1是否通过内脏神经或大脑降低体脂。PYY/GLP-1的外周作用部位将通过破坏内脏传入神经元来阻断大脑信号来测试。具体目标3：在健壮的肥胖动物模型中确定抗性淀粉是否会减少身体脂肪。将使用饮食诱导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是抗性淀粉降低体脂机制的一部分。因此，简单的饮食干预可以增加这些多肽的水平，并自然地减少身体脂肪，而不需要手术或药物手段。这个项目的独特之处在于，我们将研究营养与基因的相互作用，以测试饮食组成和能量平衡的新概念。这种饮食方法在预防人类肥胖方面具有潜在的治疗重要性。