INFLAMMATION DURING OBESITY: IMMUNE RESPONSES TO GUT ANTIGENS IN MESENTERIC FAT

肥胖期间的炎症：对肠系膜脂肪中肠道抗原的免疫反应

• 批准号: 8360250
• 负责人: Erik Eckhardt
• 金额: $ 24.68万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360250
• 关键词: Acute-Phase Proteins; Adipose tissue; Antibody Formation; Antigens; Atherosclerosis; Cardiovascular Diseases; Chronic; Dendritic Cells; Diabetes Mellitus; Diet; Disease; Fatty acid glycerol esters; Funding; Grant; Immune response; Immune system; Immunoglobulin G; Individual; Inflammation; Inflammatory; Inflammatory Response; Intake; Intestinal Absorption; Intestines; Lymphocyte; Measures; Mesentery; National Center for Research Resources; Obesity; Plasma; Principal Investigator; Research; Research Infrastructure; Resources; Risk Factors; Source; United States National Institutes of Health; Visceral; cost; cytokine; insulin signaling; macrophage; microorganism antigen; mouse model; prevent

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Sub-project 5 description BACKGROUND. Obesity is a significant risk factor for many diseases, including diabetes and atherosclerosis. Obese individuals often are in a state of chronic inflammation, with elevated plasma levels of cytokines and acute phase proteins, which hampers insulin signaling. Their adipose tissues, especially near the intestine ("visceral fat"), also are often inflamed and infiltrated with lymphocytes and macrophages. The reason for this is unknown. Our hypothesis is that high-fat diets, a common risk factor in obesity, cause (1) intestinal absorption of inflammatory microbial antigens into visceral adipose tissue and (2) a general breakdown of immunological tolerance to gut antigens, and thus chronic inflammatory responses to the microflora. DESIGN. Using mouse models, we measure intestinal absorption of antigens from the gut in relation to fat intake as well as subsequent antigen content of visceral adipose tissue. We also measure the effect of high fat diets on the intestinal mucosal immune system (predominantly dendritic cells) and on systemic antibody responses against the microflora, to determine whether excess fat intake prevents our body to contain the microflora in a non-inflammatory manner. Lastly, we are currently identifying gut bacterial species against which IgG is being formed during diet-induced obesity, in the hope to identify those species that promote inflammation during diet-induced obesity.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 次级项目5说明 背景肥胖是许多疾病的重要危险因素，包括糖尿病和动脉粥样硬化。肥胖个体通常处于慢性炎症状态，血浆细胞因子和急性期蛋白水平升高，这阻碍了胰岛素信号传导。它们的脂肪组织，特别是靠近肠道的脂肪（“内脏脂肪”），也经常发炎，并被淋巴细胞和巨噬细胞浸润。原因不明。我们的假设是，高脂饮食是肥胖症的一个常见危险因素，导致（1）肠道将炎症微生物抗原吸收到内脏脂肪组织中，（2）对肠道抗原的免疫耐受性的普遍破坏，从而导致对微生物菌群的慢性炎症反应。设计使用小鼠模型，我们测量肠道吸收的抗原从肠道的脂肪摄入量，以及随后的内脏脂肪组织的抗原含量。我们还测量了高脂肪饮食对肠粘膜免疫系统（主要是树突状细胞）和对微生物菌群的全身性抗体反应的影响，以确定过量的脂肪摄入是否会阻止我们的身体以非炎症的方式容纳微生物菌群。最后，我们目前正在鉴定在饮食诱导的肥胖症期间形成IgG的肠道细菌种类，希望鉴定在饮食诱导的肥胖症期间促进炎症的那些种类。