Adipose Tissue Hypoxia and Inflammation in Obesity

肥胖症中的脂肪组织缺氧和炎症

基本信息

批准号：
8495323
负责人：
Jianping Ye
金额：
$ 30.78万
依托单位：
LSU PENNINGTON BIOMEDICAL RESEARCH CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8495323
关键词：
Adipocytes Adipose tissue Angiogenic Factor Animals Arteries Atherosclerosis Biological Biological Markers Biological Process Biology Blindness Blood Vessels Blood flow Caloric Restriction Cessation of life Chronic Chronic Disease Data Diagnosis Diet Disease Early Diagnosis Event Exercise Failure Functional disorder Genes Growth Human Hyperglycemia Hypertension Hypoxia In Vitro Infiltration Inflammation Inflammatory Insulin Insulin Resistance Interleukin-6 Ischemia Kidney Failure Knockout Mice Knowledge Lead Leptin Lipolysis Mediating Microcirculation Mitochondria Molecular Target Mus Myocardial Infarction NF-kappa B Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity Obstructive Sleep Apnea Oxidative Stress Oxygen Oxygen measurement, partial pressure, arterial Pathogenesis Patients Plant Roots Prevention Preventive Intervention Regulation Reporting Respiration Role Signal Transduction Stream Stress Structure TNF gene Testing Therapeutic Intervention Tissues Transgenic Mice Vascular System Vasodilation Weight Gain Work abstracting adiponectin angiogenesis base constriction cytokine density design in vivo inhibitor/antagonist insulin signaling interstitial lipid biosynthesis macrophage novel p65 pressure public health relevance response restoration

项目摘要

DESCRIPTION (provided by applicant): Adipose Tissue Hypoxia and Inflammation in Obesity Abstract: Recent studies from several labs including ours consistently support that adipose tissue hypoxia (ATH) may be responsible for the initiation of chronic inflammation and adipose tissue dysfunction in obese subjects. The observations have been reported in both human and mice. The biological significance of ATH has been highlighted in several review articles about inflammation and adipose tissue function in obesity. However, the uptream and downstream events of ATH remains unknown in vivo. Based on our data, we hypothesize that the chronic inflammation represents a major event of hypoxia response in the adipose tissue in obesity. To test this hypothesis, we would propose three specific aims. AIM I. To test that adipose tissue hypoxia is a result of blood flow reduction. Blood flow and oxygen tension will be examined in adipose tissue to test the relationship in vivo. Diet-induced obese mice and ob/ob mice will be used. AIM II. To determine that the blood flow reduction is a consequence of microcirculation failure in the adipose tissue. The microcirculation will be investigated by analyzing vascular structure and function. The study will focus on angiogenesis, and vasodilation. Angiogenic factors and vessel tone regulators will be analyzed during adipose tissue growth. AIM III. To test that inflammation mediates the hypoxia signal in the regulation of adipose tissue vasculature. A role of macrophage in angiogenesis will be investigated in adipocyte-specific NF-kB p65 knockout mice. We expect that in the absence of NF-kB p65, macrophage function will be decreased in adipose tissue and angiogenesis will be defective. We expect that this study will provide a novel mechanism for chronic inflammation and adipose tissue dysfunction in obesity. Adipose tissue hypoxia has potential to be a new biomarker for early diagnosis of insulin resistance.

描述（由申请人提供）：肥胖症中的脂肪组织缺氧和炎症摘要：包括我们在内的多个实验室的最新研究一致支持脂肪组织缺氧 (ATH) 可能是导致肥胖受试者慢性炎症和脂肪组织功能障碍的原因。这些观察结果已在人类和小鼠身上都有报道。几篇关于肥胖症中炎症和脂肪组织功能的评论文章强调了 ATH 的生物学意义。然而，ATH 的上游和下游事件在体内仍然未知。根据我们的数据，我们假设慢性炎症代表肥胖脂肪组织缺氧反应的主要事件。为了检验这一假设，我们将提出三个具体目标。目的 I. 测试脂肪组织缺氧是血流量减少的结果。将检查脂肪组织中的血流量和氧张力，以测试体内的关系。将使用饮食诱导的肥胖小鼠和ob/ob小鼠。目标二。确定血流量减少是脂肪组织微循环障碍的结果。通过分析血管结构和功能来研究微循环。该研究将重点关注血管生成和血管舒张。将在脂肪组织生长过程中分析血管生成因子和血管张力调节剂。目标三。测试炎症介导脂肪组织脉管系统调节中的缺氧信号。将在脂肪细胞特异性 NF-kB p65 敲除小鼠中研究巨噬细胞在血管生成中的作用。我们预计，在缺乏 NF-kB p65 的情况下，脂肪组织中的巨噬细胞功能将下降，血管生成将有缺陷。我们期望这项研究将为肥胖症中的慢性炎症和脂肪组织功能障碍提供新的机制。脂肪组织缺氧有可能成为早期诊断胰岛素抵抗的新生物标志物。