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Role of Ileum in Reducing Obesity Related Comorbidities

回肠在减少肥胖相关合并症中的作用

基本信息

批准号：
8628249
负责人：
Rohit Kohli
金额：
$ 0.05万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8628249
关键词：
ASBT protein Acids Adolescent Adult Anatomy Animals Back Bariatrics Bile Acids Bile fluid Biliary Biliopancreatic Diversion Blood Vessels Body Weight decreased CYP7A1 gene Catheterization Childhood Cholesterol Cholic Acids Clinical Coenzyme A Comorbidity Data Diabetes Mellitus Distal Enterohepatic Circulation Fatty Liver Figs - dietary Gastric Bypass Gastroenterologist Gastrointestinal tract structure Goals Health Hepatic Hydroxycholesterols Intervention Intestinal Absorption Intestines Isotopes K-Series Research Career Programs Laboratories Length Ligaments Ligands Link Lipids Liver Malabsorption Syndromes Mass Fragmentography Measurement Measures Mediating Medical Mentors Metabolic Metabolism Modeling Morbid Obesity Non-Insulin-Dependent Diabetes Mellitus Nuclear Receptors Nutritional Obesity Obesity associated hypercholesterolemia Operative Surgical Procedures Oxidoreductase Pathway interactions Plasma Portal vein structure Positioning Attribute Prevalence Procedures Production Rattus Reporting Research Resected Resolution Role Serum Sterols Stomach Stress Surgical Models Techniques Testing Therapeutic Time Training Translating United States Weight Work absorption bariatric surgery bile acid transporter bile duct bile salts cholesterol absorption experience feeding glucose tolerance hypercholesterolemia ileum improved in vivo inhibitor/antagonist jejunum novel obesity in children professor receptor research study reuptake sham surgery

项目摘要

DESCRIPTION (provided by applicant): The prevalence of obesity is increasing at alarming rates in the United States such that bariatric surgery has become an accepted therapeutic option for adults and adolescents with morbid obesity. Bariatric surgery provides significant metabolic benefits, including resolution of type-2 diabetes and marked reduction in hypercholesterolemia, that precede the weight loss produced by these surgeries. The mechanisms responsible for these weight-independent metabolic benefits are poorly understood. Dr. Kohli's long-term research objective is to characterize the mechanisms behind these weight-loss-independent metabolic benefits of bariatric surgical procedures and translate those observations into more scalable non-invasive therapeutic measures. In this proposal Dr. Kohli will focus on the benefits of bariatric surgery to obesity related hypercholesterolemias by using a unique surgical procedure called "Ileal Transposition" in a rat model. This weight loss surgery has been previously shown to produce improved glucose tolerance similar to roux-en-y- gastric bypass without gastric size restriction or malabsorption. Dr. Kohli has generated exciting preliminary data using this surgical model that include a significant reduction in cholesterol levels that is independent of weight loss. The specific aims of his proposal will examine the mechanistic links between bile acid entero-hepatic circulation and cholesterol absorption, sensing, and endogenous production in this bariatric surgery model. He will also investigate the role of adaptation of the transposed segment of the ileum in reduction of cholesterol. These studies build on Dr. Kohli's prior work as a fellow investigating the mechanisms involved in lipid-induced nutritional stress producing hepatic steatosis. The primary goal of this mentored career development award is to provide a pathway for Dr. Kohli, a trained pediatric gastroenterologist and hepatologist, to achieve scientific independence. By developing an expertise in lipid and bile acid metabolism using small-animal surgical-obesity-intervention models, he will distinguish himself from his mentor, Professor Randy Seeley, and be well-positioned to make significant scientific and medical contributions to the understanding of obesity in children and adolescents.

描述(由申请人提供)：在美国，肥胖率正在以惊人的速度增长，以至于减肥手术已经成为患有病态肥胖的成年人和青少年的一种被接受的治疗选择。减肥手术提供了显著的代谢益处，包括2型糖尿病的解决和高胆固醇血症的显著降低，这些都先于这些手术产生的减肥效果。这些不依赖体重的代谢益处的机制还知之甚少。科利博士的长期研究目标是确定减肥外科手术的这些独立于减肥的代谢益处背后的机制，并将这些观察结果转化为更具可扩展性的非侵入性治疗措施。在这项建议中，Kohli博士将通过在大鼠模型中使用一种名为“回肠移位”的独特外科手术来关注减肥手术对肥胖相关高胆固醇血症的好处。这种减肥手术以前已经被证明可以改善葡萄糖耐量，类似于Roux-en-y胃旁路手术，而不限制胃的大小或吸收不良。科利博士使用这种外科模型产生了令人兴奋的初步数据，其中包括显著降低胆固醇水平，这与体重减轻无关。他提案的具体目标将在这个减肥手术模型中检查胆汁酸肠肝循环与胆固醇吸收、感知和内源性生产之间的机制联系。他还将研究回肠移位段的适应在降低胆固醇中的作用。这些研究建立在Kohli博士之前的工作基础上，他作为研究员研究了脂肪诱导的营养应激导致肝脏脂肪变性的机制。这个辅导式职业发展奖的主要目标是为科利医生提供一条实现科学独立的途径。科利医生是一名训练有素的儿科胃肠病和肝病专家。通过使用小动物外科肥胖干预模型发展脂肪和胆汁酸代谢方面的专业知识，他将把自己与他的导师兰迪·西利教授区分开来，并处于有利地位，为理解儿童和青少年肥胖做出重大的科学和医学贡献。