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/摘要肥胖是我们VA医疗系统中发病率和死亡率的主要原因，该系统占大多数糖尿病，高血压，冠状动脉疾病和脑血管事故的病例。通过避免严重的医疗并发症并建议采用新颖的治疗方法，对我们的老将肥胖患者的体重调节的了解将改善体重的调节。 这项研究的目的是确定高蛋白质饮食对肥胖患者的食物摄入量和体重有效，安全和有益，并在相关的实验模型中建立高蛋白饮食诱导的早期饱腹感信号的神经激素机制，重点是激活胃迷幻传统。 我们将评估高蛋白饮食对肥胖患者餐后肠荷尔蒙的饱腹感和模式的功效。一项持续24-30个月的随机对照研究将分配志愿者受试者（E30年龄，BMI 27-40 kg/m2）为：1）非常高蛋白质饮食组，2）高蛋白质饮食组和3）标准蛋白质饮食组作为对照组的对照组。所有受试者将遵循营养师，并确定循环肠激素和生化测定法。 高蛋白饮食减少食物摄入量的神经肿瘤机制将通过测试高蛋白对肥胖大鼠中肥胖大鼠的迷走神经传入satieting信号的增强作用的高度来评估，并使用药物学和电生理学方法来评估肠道肽。此外，FOS免疫组织化学以对高蛋白质饮食的措施来绘制脑神经元激活，这将使我们能够建立由高与标准蛋白质饮食激活的差异电路。 这些研究将为高蛋白饮食的体重减轻作用以及释放的餐后肠激素概况的相关变化提供临床基础，并在肥胖模型中揭示了神经元（迷神经传入）水平的潜在机制。拟议的研究将解决有关调节饱腹感/体重的机制的重要病理生理问题，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VA医疗保健系统中的一个不断升级的医疗问题。这是患者人群中慢性疾病发展的主要危险因素。这些疾病包括动脉粥样硬化，糖尿病和某些形式的癌症，因此说明了显着的发病率和死亡率。 2000年据报道，最近的一项研究确定，在93,290名美国退伍军人中，有68.4％的人至少超重，BMI> 25 kg/m2，而37.4％的BMI被归类为肥胖，而BMI超过30 kg/m2。在1,710,032名男性中，有73％的人被定义为超重，将近33％分类为肥胖。由于VA医疗保健系统的患病率正在增加，因此减少肥胖症的干预措施可能会给我们的患者群体带来积极的结果。鉴于VA医疗保健系统是美国类型中最大的，并且158个医疗机构包括超过500万名患者，降低与肥胖相关的发病率和死亡率发生率的策略不仅会通过预防对患者护理产生有益的影响，而且还会在预防中产生有益的影响，而且可以在其他方面获得大量资源，这些资源可以更好地用于Veteran Healthcare的其他方面。