Role of the lower gut in the control of energy balance

下肠道在控制能量平衡中的作用

• 批准号: 6620076
• 负责人: HENRY S KOOPMANS
• 金额: $ 13.5万
• 依托单位: UNIVERSITY OF CALGARY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6620076
• 关键词: behavior test; bioenergetics; biological signal transduction; blood tests; body weight; cell growth regulation; cholecystokinin; gastrointestinal hormones; gastrointestinal transplantation; genetic strain; hormone regulation /control mechanism; laboratory rat; large intestine; male; nerve; neuroregulation; neurotensin; nutrient intake activity; nutrition related tag; obesity; pancreas; small intestines; stomach; stomach /intestine bypass; thyroid hormones; weight loss

Surgery has been the most successful treatment for morbid obesity. The main objective of this grant proposal is to determine why lower gut signals generated in bypass surgery have been so successful in causing reduced food intake and body weight loss. We recently discovered that lower gut signals also cause a 10-25 percent increase in energy expenditure. One objective of this grant proposal is to determine how stimulation of different lengths of the ileum, caecum and colon affect energy balance and the plasma levels of the lower gut hormones: neurotensin; PYY and GLP1. Another objective is to determine the role of the extrinsic nerves to the ileum in altering food intake, energy expenditure and body weight by doing ileal transplantation surgery or denervation of the superior mesenteric nerves. A time course of the changes in energy expenditure, upper gut tissue growth and plasma lower gut hormone levels resulting from ileal transposition will be investigated in preparation for a later peptide infusion study. The role of the various macronutrients in changing energy balance and lowering body weight will be assessed by feeding various diets to rats with a 20 cm segment of ileum moved up to the mid-duodenum. The short-term objective of this research is to understand the internal control of daily intake and energy expenditure. The long-term objective is to find a medical treatment (drug or hormone analog) for obesity. In Western societies, obesity is a major medical problem that causes a great deal of human suffering. Obesity is associated with such chronic and debilitating conditions as diabetes, cancer (breast, endometrial, prostate and colon), hypertension, hyperlipidemia, stroke and heart disease. An effective medical treatment for obesity would improve the quality of life for millions of people and would reduce the cost of long-term health care.

手术一直是病态肥胖症最成功的治疗方法。 该赠款提案的主要目的是确定为什么旁路手术中产生的较低肠道信号在导致食物摄入量减少和体重减轻方面如此成功。 我们最近发现，较低的肠道信号也会导致能量消耗增加10-25％。 该赠款提案的一个目的是确定回肠，盲肠和结肠不同长度的刺激如何影响能量平衡以及下肠激素的血浆水平：神经素蛋白； PYY和GLP1。 另一个目的是通过进行回肠移植手术或对上肠系膜上神经的神经来确定外在神经对回肠的作用在改变食物摄入，能量消耗和体重。 能量消耗，上肠道组织生长和血浆下肠激素水平的变化的时间过程将进行研究，以准备后来的肽输液研究。 各种大量营养素在改变能量平衡和降低体重的作用将通过将各种饮食喂入具有20 cm的回肠段的大鼠的各种饮食来评估。 这项研究的短期目标是了解日常摄入和能量消耗的内部控制。 长期目的是为肥胖找到医疗（药物或激素类似物）。在西方社会中，肥胖是造成大量人类苦难的主要医学问题。 肥胖与糖尿病，癌症（乳腺癌，子宫内膜，前列腺和结肠），高血压，高脂血症，中风和心脏病等慢性和衰弱状况有关。 有效的肥胖症医疗将改善数百万人的生活质量，并降低长期医疗保健的成本。