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

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 子项目5说明 背景资料。肥胖是许多疾病的重要风险因素，包括糖尿病和动脉粥样硬化。肥胖者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的传递。他们的脂肪组织，特别是靠近肠道的脂肪组织(内脏脂肪)，也经常发炎，并被淋巴细胞和巨噬细胞渗透。这其中的原因不得而知。我们的假设是，高脂饮食是肥胖的常见危险因素，导致(1)肠道将炎性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普遍下降，从而导致对微生物区系的慢性炎症反应。设计。使用小鼠模型，我们测量肠道对抗原的吸收与脂肪摄入量的关系，以及随后内脏脂肪组织的抗原含量。我们还测量了高脂肪饮食对肠道粘膜免疫系统(主要是树突状细胞)和针对微生物区系的系统抗体反应的影响，以确定过量脂肪摄入是否阻止我们的身体以非炎症方式遏制微生物区系。最后，我们目前正在鉴定饮食诱导肥胖期间针对其形成免疫球蛋白的肠道细菌种类，希望确定那些在饮食诱导肥胖过程中促进炎症的种类。

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.