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:
    7683738
  • 负责人:
  • 金额:
    $ 32.38万
  • 依托单位:
  • 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

项目摘要

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, arterio- sclerotic 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 availably 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] Patho- genetic 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.
肥胖症每年造成超过300,000人死亡和1,170亿美元的医疗费用,但大部分 我们对其病理生理学的理解源于啮齿动物的研究。减肥手术提供了最好的 目前的治疗方法是减肥和改善合并症(例如糖尿病) 肥胖症中度的患者,但一直是高风险手术,发病率明显和死亡率 在较高的肥胖等级中。肥胖合并症,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疾病(NAFLD)具有常见的病原体 涉及胰岛素抵抗的机制。反过来,这与不完全理解的方式有关 肥胖中典型的“代谢综合征”的代谢活性,腹内脂肪库, 这些仓库和肝脏之间的长链脂肪酸(LCFA)的运动,以及LCFA的“脂毒性” 对于关键的非辅导组织,例如胰腺β细胞。我们已经开发了一个新颖的两个阶段 高度肥胖症的腹腔镜手术方法。在 -100 IB体重减轻,当患者是更好的手术风险时,通过第二个手术 吸收不良。我们最初的一系列高风险患者(BMI> 50)已增长到100例,长长的病例 定期体重减轻,发病率最小,没有死亡率,因此这种方法已成为我们对待 所有BMI> 60的患者以及BMI> 50加上其他风险因素的患者的选择。在这种情况下可用 每次手术时肝和皮下脂肪的成对活检的患者将使我们能够 研究肥胖和体重减轻的影响首次研究:[a]脂肪组织的关键方面 生物学,包括对脂肪细胞LCFA摄取和脂解的特异性作用,内分泌功能 脂肪细胞,以及巨噬细胞浸润和脂肪因子的产生对这些功能的影响; [b]病情 - NAFLD的遗传机制,包括肝细胞壁LCFA和甘油三酸酯(TG)摄取的研究,LCFA 合成和氧化,脂蛋白合成和TG排泄;和[C]动脉粥样硬化的发病机理 肥胖症的血脂异常(TG升高,HDL降低)。研究将记录在 人类和啮齿动物之间肥胖的病理生理学,并应产生新颖的见解,并具有潜力 治疗意义,使其主要合并症的机制。

项目成果

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PAUL David BERK其他文献

PAUL David BERK的其他文献

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{{ truncateString('PAUL David BERK', 18)}}的其他基金

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
  • 批准号:
    8004314
  • 财政年份:
    2010
  • 资助金额:
    $ 32.38万
  • 项目类别:
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
  • 批准号:
    7100776
  • 财政年份:
    2006
  • 资助金额:
    $ 32.38万
  • 项目类别:
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
  • 批准号:
    7283633
  • 财政年份:
    2006
  • 资助金额:
    $ 32.38万
  • 项目类别:
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
  • 批准号:
    7480957
  • 财政年份:
    2006
  • 资助金额:
    $ 32.38万
  • 项目类别:
Bariatic Surgery: Outcomes & Impact on Pathophysiology
减肥手术:结果
  • 批准号:
    6734121
  • 财政年份:
    2003
  • 资助金额:
    $ 32.38万
  • 项目类别:
Bariatic Surgery: Outcomes & Impact on Pathophysiology
减肥手术:结果
  • 批准号:
    6941873
  • 财政年份:
    2003
  • 资助金额:
    $ 32.38万
  • 项目类别:
Bariatric Surgery: Outcomes & Impact on Pathophysiology
减肥手术:结果
  • 批准号:
    8119122
  • 财政年份:
    2003
  • 资助金额:
    $ 32.38万
  • 项目类别:
Bariatric Surgery: Outcomes & Impact on Pathophysiology
减肥手术:结果
  • 批准号:
    8727908
  • 财政年份:
    2003
  • 资助金额:
    $ 32.38万
  • 项目类别:
Bariatic Surgery: Outcomes & Impact on Pathophysiology
减肥手术:结果
  • 批准号:
    7122447
  • 财政年份:
    2003
  • 资助金额:
    $ 32.38万
  • 项目类别:
Bariatic Surgery: Outcomes & Impact on Pathophysiology
减肥手术:结果
  • 批准号:
    6945933
  • 财政年份:
    2003
  • 资助金额:
    $ 32.38万
  • 项目类别:

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腹股沟白色脂肪组织中米色脂肪细胞可塑性的调节。
  • 批准号:
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