Bariatric Surgery for Morbid Obesity: Clinical and Pathophysiologic Consequences

病态肥胖的减肥手术：临床和病理生理学后果

基本信息

批准号：
7283633
负责人：
PAUL David BERK
金额：
$ 33.16万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-15 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7283633
关键词：
Abbreviations Adipocytes Adipose tissue Anabolism Animal Model Animals Apolipoprotein A-I Apolipoproteins Apolipoproteins B Arteriosclerotic Cardiovascular Disease Atherosclerosis B-Lymphocytes Bariatrics Binding Binding Proteins Biological Assay Biology Blood Blood specimen Body Weight decreased CETP gene Carbohydrates Catabolism Cell Size Cessation of life Characteristics Cholesterol Cholesterol Ester Transfer Proteins Clinical Comorbidity Data Defect Descriptor Diabetes Mellitus Down-Regulation Dyslipidemias Endocrine Enzymes Epidemic Excretory function Fasting Fatty Liver Fatty acid glycerol esters Fatty-acid synthase Functional disorder Gastrectomy Gene Expression Gene Targeting Genes HDL-triglyceride Harvest Hepatic Hepatocyte High Density Lipoproteins Human Hyperlipidemia Hypertension Hypertriglyceridemia Infiltration Inflammatory Insulin Insulin Resistance Intra-abdominal Kinetics Lead Leptin Lipase Lipolysis Lipoprotein Receptor Lipoproteins Liver Liver diseases Low-Density Lipoproteins Malabsorption Syndromes Measurement Medical Messenger RNA Metabolic syndrome Metabolism Morbid Obesity Morbidity - disease rate Movement Non-Insulin-Dependent Diabetes Mellitus Obesity Oleic Acid Oleic Acids Operative Surgical Procedures Outcome PPAR gamma Pathogenesis Pathway interactions Patients Phospholipid Transfer Proteins Physiological Processes Plasma Population Procedures Production Protein Secretion Proteins Protocols documentation RNA Rate Regulatory Element Relative (related person)Research Personnel Response Elements Risk Risk Factors Rodent SR-BI receptor Sampling Series Severities Source Staging Stearoyl-CoA Desaturase Sterols Stromal Cells Structure of beta Cell of islet Testing Therapeutic Time Transferase Triglycerides Very low density lipoprotein abdominal fat activator 1 protein adiponectin bariatric surgery cost cytokine density falls fatty acid metabolism fatty acid oxidation hepatic lipase human CETP protein insight interest lipoprotein triglyceride liver biopsy long chain fatty acid mRNA Expression macrophage man microsomal triglyceride transfer protein moderate obesity mortality non-alcoholic fatty liver novel novel therapeutics obesity treatment oxidation phospholipid exchange proteins programs receptor response size subcutaneous therapeutic target uptake

项目摘要

DESCRIPTION (provided by applicant): Obesity is responsible for more than 300,000 deaths and $117 billion in medical costs annually, but much of our understanding of its pathophysiology derives from studies in rodents. Bariatric surgery offers the best current treatment results in terms of weight-loss and improvement in co-morbidities such as diabetes in patients with moderate obesity, but has been a high risk procedure, with appreciable morbidity and mortality in higher obesity grades. Among obesity co-morbidities, diabetes, hypertension, dyslipidemia, arteriosclerotic cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD) have common pathogenetic mechanisms involving insulin resistance. This, in turn, relates in incompletely understood ways to the large, metabolically active, intra-abdominal fat depots typical of the "metabolic syndrome" in the obese, the movement of long chain fatty acids (LCFA) between these depots and the liver, and the "lipotoxicity" of LCFA for key non-adipose tissues, e.g. the pancreatic beta-cell. We have developed a novel two-stage laparoscopic surgical approach to high-grade obesity. A restrictive sleeve gastrectomy is followed after a (100 Ib weight loss, when the patient is a better surgical risk, by a second procedure that causes malabsorption. Our initial series of high risk patients (BMI >50) has grown to 100 cases with excellent long term weight loss, minimal morbidity, and no mortality, so that this approach has become our treatment of choice for all patients with BMI > 60 and those with BMI >50 plus other risk factors. The availability in such patients of paired biopsies of liver and of omental & subcutaneous fat at each operation will allow us to study, for the first time in man, the effects of obesity and weight loss on: [A] Key aspects of adipose tissue biology, including depot-specific effects on adipocyte LCFA uptake and lipolysis, endocrine functions of the adipocyte, and the impact of macrophage infiltration and adipokine production on these functions; [B] Pathogenetic mechanisms of NAFLD, including studies of hepatocellular LCFA and triglyceride (TG) uptake, LCFA synthesis and oxidation, lipoprotein synthesis and TG excretion; and [C] Pathogenesis of the atherogenic dyslipidemia (elevated TG, reduced HDL) of obesity. The studies will document important differences in the pathophysiology of obesity between humans and rodents, and should yield novel insights, with potential therapeutic implications, into mechanisms responsible for its key comorbidities.

描述（由申请人提供）：肥胖症每年造成超过300,000人的死亡和1,170亿美元的医疗费用，但我们对其病理生理学的大部分理解都来自啮齿动物的研究。减肥手术在体重减轻和合并症的改善方面提供了最佳的当前治疗结果，例如中度肥胖症患者的糖尿病，但一直是高风险手术，在较高的肥胖等级中具有明显的发病率和死亡率。在肥胖合并症中，糖尿病，高血压，血脂异常，动脉硬化心血管疾病和非酒精性脂肪肝病（NAFLD）具有涉及胰岛素抵抗的常见病原机制。反过来，这与肥胖中“代谢综合征”的典型的大型，代谢，腹腔内脂肪仓库的方式不完全理解有关，这些depots和肝脏之间的长链脂肪酸（LCFA）的运动以及LCFA的“脂肪毒性”的非脂蛋白毒性在非脂肪毒性的运动中，用于非脂肪毒素的非脂肪毒性。胰腺β细胞。我们已经开发了一种新型的两阶段腹腔镜外科手术方法，用于高级肥胖症。在A（100 IB减肥，患者是更好的手术风险）之后，通过引起吸收不良的第二个程序进行限制性袖子胃切除术。我们最初的高风险患者（BMI> 50）的最初系列已经成长为100例长期体重降低的长期体重，不可能及时享受BM的治疗因素，而BM的患者不再有50次，而BM的患者均可及其> 50;这类患者在每个手术中对肝脏成对活检以及胶质和皮下脂肪的可用性将使我们能够在人类中首次研究肥胖和体重减轻的影响：[a]脂肪组织生物学的关键方面，包括脂肪特异性的影响，包括对脂肪细胞对脂肪的lcfa摄取和脂肪分解的影响，并构成了载脂的功能，并且是对载脂的影响。这些功能的浸润和脂肪因子的产生；肥胖症的动脉粥样硬化血脂异常（升高，HDL降低）的[C]发病机理。这些研究将记录人类和啮齿动物之间肥胖的病理生理学的重要差异，并应产生新的见解，具有潜在的治疗意义，以使其关键合并症的机制。