Gastrointestinal Hormonal Regulation of Obesity

肥胖的胃肠激素调节

• 批准号: 7862225
• 负责人: JOSEPH R PISEGNA
• 金额: --
• 依托单位: VA GREATER LOS ANGELES HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-10-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7862225
• 关键词: Accounting; Address; Adult; Age; American; Animal Model; Animals; Appetite Regulation; Arteriosclerosis; Autonomic nervous system; Behavior Therapy; Biochemical; Biolectric Impedance; Biological Assay; Body Weight; Body Weight decreased; Brain; Brain Mapping; Bursitis; Calories; Caring; Cell Nucleus; Cells; Cellular biology; Chemicals; Cholecystokinin; Chronic Disease; Clinical; Clinical Treatment; Clinical Trials; Colorectal Cancer; Comorbidity; Complex; Coronary Arteriosclerosis; Cumulative Trauma Disorders; Data; Degenerative polyarthritis; Desire for food; Development; Diabetes Mellitus; Diet; Diet Modification; Dietary Proteins; Dietitian; Disease; Dorsal; Duodenum; Dyslipidemias; Eating; Endocrine; Esthesia; Exercise; Experimental Models; Feeding behaviors; Functional disorder; Gastrointestinal Hormones; Gastrointestinal Motility; Gastrointestinal tract structure; Gastroparesis; General Population; Goals; Health; Health Care Costs; Health Services; Health Services Research; Healthcare; Healthcare Systems; Hormonal; Hormones; Human; Hypertension; Immunohistochemistry; In Vitro; Incidence; Ingestion; Intervention; Knowledge; Leptin; Link; Los Angeles; Macronutrients Nutrition; Malignant Neoplasms; Malignant neoplasm of pancreas; Measures; Mediating; Medical; Medical center; Metabolic; Methods; Modeling; Molecular Biology; Morbidity - disease rate; Neural Pathways; Neuroendocrine Tumors; Neurons; Neuropeptides; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Obesity; Orthopedics; Outcome; Overweight; Pathway interactions; Patient Care; Patients; Pattern; Peptides; Peripheral; Physiological; Play; Population; Preparation; Prevalence; Prevention; Protein Hydrolysates; Proteins; Quality of life; Questionnaires; Randomized Controlled Trials; Rattus; Recording of previous events; Reducing diet; Regulation; Reporting; Research Personnel; Resources; Risk; Risk Factors; Role; Satiation; Savings; Sensory; Serum; Signal Transduction; Stimulus; Stomach; Stroke; Surgical complication; System; Taste Perception; Testing; United States; Vagus nerve structure; Vesicle; Veterans; Weight; Weight Gain; Woman; abstracting; anorexigenic peptide; base; care systems; cell motility; des-n-octanoyl ghrelin; energy balance; gastric secretion substance; gastrointestinal; ghrelin; glucagon-like peptide 1; hormone regulation; improved; in vivo; innovation; interdisciplinary collaboration; medical complication; men; mortality; neurophysiology; novel therapeutic intervention; obesity treatment; patient population; primary outcome; programs; sensor; translational approach; treatment strategy; volunteer

DESCRIPTION (provided by applicant): Project Summary/Abstract Obesity is a major cause of morbidity and mortality within our VA medical system accounting for the majority of cases of diabetes mellitus, hypertension, coronary artery disease and cerebrovascular accidents. An improved understanding of the regulation of body weight in our veteran obese patients will improve the quality of life by avoidance of serious medical complications and by suggesting novel therapeutic approaches. The objective of this study is to establish that a high protein diet is efficacious, safe and beneficial to curtail food intake and body weight in obese patients and to establish the neurohormonal mechanisms of high protein diet-induced early satiety signal in relevant experimental model, focusing on activation of gastric vagal afferents. We will assess the efficacy of a high protein diet on satiety and pattern of postprandial gut hormone in obese patients. A randomized controlled study lasting 24-30 months will assign volunteer subjects (ages e30, BMI 27-40 kg/m2) to: 1) Very high protein diet group, 2) High protein diet group, and 3) Standard protein diet group as control with same calories. All the subjects will be followed by a dietitian and determination of circulating gut hormone and biochemical assays will be performed. Neurohumoral mechanisms through which high protein diet curtailed food intake will be assessed by testing the hypthesis of a potentiating effect of gut peptides released by high protein on vagal afferent satieting signaling to the brain in obese rats using pharmacologica and electrophysiologic approaches. In addition Fos immunohistochemistry to map brain neuronal activation in respone to high protein diet will allow us to establish differential circuitries activated by high vs standard protein diet. These studies will provide a clinical basis on the weight reducing effect of high protein diet and the associated alterations in the profile of postprandial gut hormones released, and unravel the underlying mechanisms at the neuronal (vagal afferent) level in an expermental model of obesity. The proposed studies will address important pathophysiological questions regarding the mechanisms regulating satiety/body weight as well as provide potentially important clinical treatment strategies. PUBLIC HEALTH RELEVANCE: NARRATIVE Obesity is an escalating medical problem in the VA Healthcare System. It is a major risk factor for the development of chronic diseases seen in our patient population. These illnesses include arteriosclerosis, diabetes mellitus and certain forms of cancer and, therefore, accounts for significant morbidity and mortality. A recent study, reported in 2000, established that among 93,290 women American veterans, 68.4% were at least overweight with a BMI >25 kg/m2 and 37.4% were classified as obese with a BMI over 30 kg/m2. Of 1,710,032 men 73% were defined as overweight and nearly 33% were classified as obese. Since the prevalence is increasing in the VA Healthcare System, interventions to reduce obesity are likely to result in positive outcomes for our patient population. Given that the VA Medical Care System is the largest of its type in the USA, and that the 158 medical facilities include over 5 million patients, strategies to reduce the incidence of obesity-related morbidity and mortality are likely to have a beneficial impact not only on patient care through prevention but will result in a significant savings in resources that could be better spent on other aspects of veteran healthcare.

描述(由申请人提供)： 项目摘要/摘要肥胖是退伍军人医疗系统中发病率和死亡率的主要原因，占糖尿病、高血压、冠状动脉疾病和脑血管意外的大部分。更好地了解我们的老年肥胖患者的体重调节将通过避免严重的医疗并发症和提出新的治疗方法来提高生活质量。本研究的目的是证实高蛋白饮食对肥胖患者减少食物摄入量和体重是有效、安全和有益的，并在相关实验模型上建立高蛋白饮食诱导早饱信号的神经激素机制，重点是激活胃迷走神经传入。我们将评估高蛋白饮食对肥胖患者的饱腹感和餐后胃肠激素模式的影响。一项为期24-30个月的随机对照研究将志愿者(年龄E30岁，体重指数27-40 kg/m2)分配到：1)极高蛋白饮食组，2)高蛋白饮食组，3)标准蛋白质饮食对照组，热量相同。所有受试者都将接受营养师的指导，并将进行循环肠道激素测定和生化分析。高蛋白饮食减少食物摄入量的神经体液机制将通过药理学和电生理学方法测试高蛋白释放的肠肽对肥胖大鼠迷走神经传入满足信号到大脑的增强作用来评估。此外，Fos免疫组织化学定位高蛋白饮食对脑神经元激活的反应，将使我们能够建立高蛋白饮食和标准蛋白饮食激活的不同回路。这些研究将为高蛋白饮食的减肥效果和餐后胃肠激素释放谱的相关变化提供临床基础，并在神经元(迷走神经传入)水平上揭示肥胖实验模型的潜在机制。拟议的研究将解决有关饱腹感/体重调节机制的重要病理生理学问题，并提供潜在的重要临床治疗策略。 公共卫生相关性： 叙事肥胖是退伍军人管理局医疗系统中一个日益严重的医疗问题。它是在我们的患者群体中看到的慢性疾病发展的主要风险因素。这些疾病包括动脉硬化、糖尿病和某些形式的癌症，因此造成了严重的发病率和死亡率。2000年报道的一项最新研究表明，在93290名美国退伍军人中，68.4%的人至少超重，体重指数为25公斤/平方米，37.4%的人被归类为肥胖，体重指数超过30公斤/平方米。在1710,032名男性中，73%被定义为超重，近33%被定义为肥胖。由于退伍军人医疗保健系统中的患病率正在上升，减少肥胖的干预措施可能会为我们的患者群体带来积极的结果。鉴于退伍军人医疗保健系统是美国同类医疗系统中规模最大的，而且158家医疗机构包括500多万名患者，降低肥胖相关发病率和死亡率的策略可能不仅会通过预防对患者护理产生有益影响，还将显著节省资源，这些资源本可以更好地用于退伍军人医疗保健的其他方面。